Albert & Jakobiec's Principles & Practice of Ophthalmology, 3rd Edition

CHAPTER 181 - Retinoschisis

Tatsuo Hirose,
Barbara A. Blodi

Retinoschisis is the splitting (schisis) of the neural retinal layer, which is embryologically derived from the inner layer of the optic cup.[1] Although retinoschisis resembles retinal detachment in that both show retinal elevation in the ocular fundus, the latter is an actual separation of the neural retinal layer from the pigment epithelium, which is derived from the outer layer of the optic cup.

Retinoschisis can be classified into three categories: acquired (senile, degenerative), congenital (juvenile, hereditary, develop-mental), and secondary, in which splitting of the neural retina occurs as a result of, or in association with, primary fundus disease or trauma.[2]

ACQUIRED RETINOSCHISIS

The most common type of retinoschisis is acquired retinoschisis, which is found in 4-22% of the normal population older than 40 years[3-5] and usually affects both sexes equally. Ophthalmologists conducting a population-based study in Copenhagen examined 946 patients with a Goldmann 3-mirror lens and with ultrasound for the prevalence and progression of peripheral retinoschisis over a period of 14 years (1986-2000). The prevalence of retinoschisis in one or both eyes was 3.9%[6] in persons aged 60-80 years. For 73.7% of patients, the retinoschisis remained stable during follow-up. The retinal quadrant most commonly involved was the inferior temporal quadrant (44.4%).

Previously called senile retinoschisis,[1] acquired retinoschisis usually affects persons older than 50 years. Although rare, this type of retinoschisis can be found in patients in their 20s and 30s, making it more appropriately termed acquired rather than senile.[7] Splitting in acquired retinoschisis occurs in the outer plexiform layer,[8] or occasionally in the inner nuclear layer,[9] as a result of confluence of the area of cystoid degeneration. Histologically, two types of acquired retinoschisis are seen, one relatively flat, which is called reticular cystoid degeneration, and the other bullous.[8] However, clinical distinctions between the two are not always easy to make, and the two types are often seen in the same eye. Because retinoschisis starts from the extreme peripheral fundus near the ora serrata, usually in a lower temporal quadrant, patients commonly have no visual symptoms except in the most advanced stages of the disease.

CLINICAL FEATURES

Ophthalmoscopically, early acquired retinoschisis appears as a flat, smooth, retinal elevation that is best appreciated when the area is viewed tangentially with a binocular indirect ophthal-moscope using scleral depression. The elevated retina, which represents an inner layer of the retinoschisis, always contains retinal blood vessels, some of which appear white in the periphery as though they were occluded (Fig. 181.1). A number of small, shiny, yellow-white dots, resembling snowflakes, are observed on the elevated retinal surface. These dots may represent the footsteps of the pillars of the Müller cells.

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FIGURE 181.1  Fundus drawing of acquired retinoschisis.

 

 

Retinoschisis usually remains stationary over many years; a spontaneous collapse may occur, but this is rare.[9, 10] In some cases, retinoschisis expands in three directions: toward the posterior pole, circumferentially along the ora serrata, and toward the vitreous cavity, increasing the height of the elevation. In an advanced stage, retinoschisis forms a large, fixed, ballooning elevation of the inner layer that appears almost transparent. The surface is smooth and does not undulate (Fig. 181.2). The presence of an outer layer of retinoschisis is demonstrated by a white-with-pressure sign on indirect ophthalmoscopy with scleral depression. The outer layer often has multiple, reddish, round spots that resemble clusters of fish or frog eggs (Fig. 181.3). The inner layer also has a pitted appearance on its back, which is best appreciated by slit-lamp examination with retroillumination. Cases in which retinoschisis reaches the macula are rare. Concomitant age-related macular degeneration may be found because of the advanced age of patients. A break or breaks may be found in one or both layers of retinoschisis (Fig. 181.4). The outer layer break tends to be single and larger and is found more frequently than the inner layer break, which tends to be small.

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FIGURE 181.2  Fundus photograph of relatively advanced stage of acquired retinoschisis.

 

 

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FIGURE 181.3  Fundus photograph of the outer layer of acquired retinoschisis shows multiple pits with a fish- or frog-egg appearance.

 

 

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FIGURE 181.4  Cross-section of the eye with retinoschisis shows breaks in the outer and inner layers.
From Shea M, Schepens CL, von Pirquet SR: Retinoschisis. I: Senile type. Arch Ophthalmol 1960; 63:1. Copyright 1960, American Medical Association.

 

 

Retinal detachment may develop in the eye with acquired retinoschisis as a complication of the retinoschisis or as a result of a full-thickness retinal break located in the area unaffected by retinoschisis. The inner layer break(s) alone does not cause retinal detachment. A break or breaks in the outer layer alone or in both layers may lead to retinal detachment (Figs 181.5 and 181.6). When the retinoschisis is limited to the area anterior to the equator, usually no field defect is detected. If the retinoschisis extends posterior to the equator, it usually causes a field defect that is an absolute scotoma, with its edge of different isopters very sharp or steep. The visual-field defect isusually seen in the superonasal quadrant, corresponding to the retinoschisis located in the inferotemporal quadrant. The field defect that results from retinal detachment has a sloping border, unless the detachment is long-standing. The simple indirect ophthalmoscopic perimetry reported by Kyostra and Holdren also may aid in diagnosis: while performing the indirect ophthalmoscopy, a shadow is projected onto the retinoschisis by holding a scleral depressor on the examiner's side of the condensing lens. The patient is then asked whether she or he can see a black object from the projected scleral depressor. Patients with retinoschises answer no; patients with retinal detachment respond positively.[11] Whether this test works in patients with a long-standing retinal detachment with very thin atrophic retina remains to be seen.

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FIGURE 181.5  Probable mechanism of the development of a full-thickness retinal detachment from the outer layer break without an inner layer break in retinoschisis. (a) Ballooning retinoschisis. (b) Outer layer and surrounding full-thickness retina are elevated. The detached outer layer becomes thin and stretched (arrows). (c) Outer layer breaks at or near the edge of the retinoschisis drive the fluid (arrow) into the subretinal space. There is no communication between the vitreous cavity and the subretinal space. Retinal detachment remains localized.

 

 

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FIGURE 181.6  Probable mechanism of development of a retinal detachment from the breaks in both layers of retinoschisis. (a) Retinoschisis with breaks in both layers without retinal detachment. The vitreous gel may be in contact with the inner layer break. (b) When the liquid vitreous is in contact with the inner layer break, a full-thickness retinal detachment can result (arrows). (c) Retinal detachment can become quite extensive, sometimes total, because the vitreous cavity and subretinal space are connected by the breaks in both layers of the retinoschisis.

 

 

 

 

DIFFERENTIAL DIAGNOSIS

Retinoschisis may still be misdiagnosed as a retinal detachment; conversely, a long-standing inferior retinal detachment can be mistaken for retinoschisis. In rhegmatogenous retinal detachment, the detached retina is less transparent, undulates, and is typically mobile, forming large folds or multiple minute folds called shagreen; subretinal fluid may shift with a change in position of the patient's head. In retinoschisis, the surface is smooth and the height of the elevation stays the same regardless of the patient's head position. If a horseshoe tear or a break with an operculum is found in the elevated portion of the retina, the elevation is probably retinal detachment rather than retinoschisis, because a horseshoe tear or an operculum with a break rarely forms in the inner layer of retinoschisis. Vitreous hemorrhage is equally rare in acquired retinoschisis. If it happens, it is probably not the result of the retinal tear in the inner layer, but rather a concomitant posterior vitreous detachment[12] or a full-thickness retinal tear outside the area of retinoschisis. One application of photocoagulation to the bare pigment epithelium through the detached retina causes no reaction or a very faint gray-yellow reaction. The same application to the intact outer layer of retinoschisis causes a white coagulation mark. The B-scan ultrasonogram with scleral depression may also help to differentiate the two, particularly when the fundus view is limited. Besides a smooth, thin, flat, or convex immobile membrane in the periphery that does not reach the optic disk found by B-scan, the scleral depression in the area of the abnormality does not flatten or only slightly flattens the elevation in the case of retinoschisis. If the membrane seen in the B-scan is a rhegmatogenous retinaldetachment, the space between the sclera and the elevated retina flattens as the subretinal fluid escapes through the retinal break on scleral indentation.[13] The technique is less useful when the retina is highly elevated. In addition, optical coherence tomography can differentiate retinoschisis from shallow full thickness retinal detachment as eyes with retinoschisis will show evidence of the outer retina still adherent to the retinal pigment epithelium.[14]

These clinical features, which may help differentiate retinal detachment from retinoschisis, are listed in Table 181.1. However, these criteria are not absolute; exceptions exist. For instance, photocoagulation may not produce a white mark on the outer layer of the retinoschisis if the layer is atrophic or extensively degenerated. The field defect in retinal detachment usually slopes at the edge, but in long-standing retinal detachment the border of the field defect may be sharp and the defect absolute, resembling the field defect in retinoschisis.


TABLE 181.1   -- Differentiating Retinal Detachment and Retinoschisis

Characteristic

Retinal Detachment

Retinoschisis

Transparency

Little

Much

Mobility

Mobile

Immobile

Surface

Folds

Smooth

Fluid shift

Often present

Absent

Horseshoe tear, break with operculum

Common

Rare

Reaction to photocoagulation

Absent or faint

Whiten, rarely absent

Field defect

Sloping border

Sharp border

Ultrasonogram with scleral depression

Becomes shallow

Unchanged

 

 

 

NATURAL HISTORY

Acquired retinoschisis generally remains stable without causing any visual impairment. Spontaneous flattening of the retinoschisis does occur, although it is rare, as mentioned previously. In a small percentage of patients, the retinoschisis does progress. Among 245 eyes with uncomplicated retinoschisis followed up for 1 month to 15 years without treatment, 33 eyes (13.5%) showed progression from 1 month to 10 years. In these eyes, the retinoschisis expanded or formed a new break in one or both layers of the retinoschisis. The progression is usually slow, withsignificant expansion taking months or years. Figure 181.7 illustrates how retinoschisis located in the inferotemporal periphery in 13 eyes extended over a long observation period. Figure 181.8 illustrates the extension of retinoschisis in nine eyes in which the condition started in the superotemporal quadrant. The speed of progression varies from patient to patient; even the fastest-growing progression reaching inside the major vascular arcade from the equator took 7 years.

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FIGURE 181.7  Composite drawing of the extent of progressive retinoschisis in 13 eyes on the initial and the last examinations. Retinoschisis started in the inferotemporal quadrant. Numbers next to arrows indicate the follow-up periods in years except for one number (8) followed by m (months). Arrows indicate the extent of progression.
From Hirose T, Marcil G, Schepens CL, et al: Acquired retinoschisis: observations and treatment. In: Pruett RC, Regan CDJ, eds. Retina Congress. Norwalk, CT: Appleton-Century-Crofts; 1972:489.

 

 

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FIGURE 181.8  Composite drawing of the extent of progressive retinoschisis that started in the superotemporal quadrant in nine eyes. Arrows indicate the extent of progression. Numbers next to arrows indicate the follow-up periods in years except for one number (8) followed by m (months).
From Hirose T, Marcil G, Schepens CL, et al: Acquired retinoschisis: observations and treatment. In: Pruett RC, Regan CDJ, eds. Retina congress. Norwalk, CT: Appleton-Century-Crofts; 1972:489.

 

 

 

 

MANAGEMENT

The management of acquired retinoschisis requires bilateral fundus drawings and visual-field plotting. The extent of retinoschisis should be marked in relation to the adjacent fundus landmarks, such as branches of the retinal vessels or vortex ampulla. A good initial fundus drawing helps the examiner determine whether the retinoschisis has expanded at the follow-up visit. Fundus photograph localization is not useful in the early stage of retinoschisis because of its peripheral location and the small degree of elevation of the lesion. If the retinoschisis is relatively flat without any break and is limited to the area anterior to the equator, the examination is repeated in a year. In such a case, retinoschisis is probably a fiding incidental to the reason for the ocular examination. If the retinoschisis has a break or breaks in one of the layers or is already extended posterior to the equator, reexamination is recommended in 3-6 months, depending on the severity of the lesions; examination should take place sooner if the patient notices symptoms such as floaters or visual disturbances. If there is no change in the retinoschisis at the second visit, the schedule of annual examinations should be continued until otherwise indicated. Indications for treatment of acquired retinoschisis are controversial.

Because the incidence of acquired retinoschisis is relatively high among the normal population and visual disturbances caused by retinoschisis or complications thereof are relatively rare, and because treatment is not always effective or can be met with serious complications, treatment is not recommended for patients with peripheral retinoschisis.

After following up 218 eyes with retinoschisis for an average of 9.1 years, Byer did not fid a single eye with subjectively impaired vision from either extension of retinoschisis or development of retinal detachment, although he determined that the original retinoschisis had expanded in 3.2-6.4% of patients or had formed new breaks in 6.4% of eyes.[15] From this observation, he concluded that no treatment is needed unless retinoschisis is associated with a symptomatic progressive retinal detachment, which he did not observe in his patients.[15]

The study statistics vary depending on the patient population. A study performed in a normal population or in patients seeking refraction from a primary care ophthalmologist would result in a different conclusion from that in a study of patients examined by tertiary-care retinal specialists. Patients who experience serious complications of retinoschisis may not remain in the care of their primary physician, possibly biasing the statistics. Conversely, patients who display early acquired retinoschisis diagnosed by a tertiary-care physician may have other conditions or symptoms unrelated to the retinoschisis. However, it is unknown whether the presence of other retinal or vitreous abnormalities, such as age-related macular degeneration, affects the natural course of retinoschisis. Statistics are helpful in the overall view of the nature of retinoschisis; however, each case requires individual management.

It is well known that extensive retinal detachment and very posteriorly extended retinoschisis cause irreparable visual-field defects whether or not patients have visual complaints. It is generally true that uncomplicated retinoschisis is asymptomatic even when it balloons or extends posteriorly in the fundus. Patients often experience symptoms when retinal detachment develops; however, they may be unaware of symptoms despite the presence of retinal detachment. This typically is seen in those detachments associated with dialysis in young individuals. This type of retinal detachment is usually located in the inferotemporal quadrant; the affected patients are often asymptomatic, and they do not seek medical care until detachment extends close to the macula. Multiple subretinal demarcation lines and secondary retinal cysts, often found in the patients with dialysis, indicate that the retinal detachment is long-standing. Such a case should not be confused with the retinal detachment in young patients with dialysis without any sign of acquired retinoschisis. The cause of retinal dialysis in young patients is unknown. Most dialysis in young patients is probably unrelated to retinoschisis. However, evidence suggests that some dialysis in young patients results from breaks that developed in both layers at the ora serrata in acquired retinoschisis.[16-18] As shown in Figure 181.9, the dialysis may not be a single full-thickness retinal break formed at the ora serrata. Careful examination reveals that the dialysis is composed of two breaks in two retinal layers, strongly suggesting that this dialysis, or break at the ora serrata, represents breaks in both layers of the retinoschisis. Because of the extensive and highly elevated retinal detachment, it cannot be determined where the retinoschisis ends and the retinal detachment starts. However, it is obvious in this case that the retinal detachment was caused by breaks at the ora serrata in acquired retinoschisis. No one would question the necessity of operating on such a retinal detachment, which probably originated from retinoschisis, although this detachment may be asymptomatic.

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FIGURE 181.9  Fundus drawing of a retinal detachment in a young patient with dialysis. The retinal dialysis probably represents breaks in both layers of retinoschisis formed at the ora serrata, as shown in the schema (bottom right) of the cross-sectional view through the arrow.

 

 

A case was also reported in which an asymptomatic full-thickness retinal detachment developed as the result of a large outer layer break and small, multiple inner layer breaks.[19] This eye was operated on successfully before the detachment extended to the macula.[19] Therefore, the retinal detachment that develops as a complication of acquired retinoschisis is not always symptomatic. Furthermore, although quite rare, acquired retinoschisis does extend to the posterior pole.[20, 21] Some authors challenged this by stating that these cases may not be actual retinoschisis involving the macula but rather retinal detachment in the macula caused by the posteriorly located outer layer break.[22] However, it is highly unlikely that the outer layer breaks were missed by these authors. Retinoschisis that has encroached on the posterior pole is well documented during the course of observation and should be considered a potential candidate for treatment, although it may be asymptomatic. At the combined meeting of the Retina Society and the Club Jules Gonin in Bern, Switzerland, in September 1996, Wilson reported the results of a survey of 344 Retina Society members, most of whom were US members, concerning the management of acquired retinoschisis. Sixty percent of the members responded. The survey reported 87 cases of foveal extension of retinoschisis without retinal detachment. (Wilson RS: The management of progressive acquired retinoschisis and collapse of cavities: A survey of the Retina Society. 20th meeting of the Club Jules Gonin and 29th Annual scientific session of the Retina Society P14, Bern, Switzerland, 1996 (personal communication). Literature on foveal extension of acquired retinoschisis is scanty. Obviously, there are many unreported cases.

Retinoschisis may already have extended quite posteriorly in the fundus with a large field defect at the time of initial examination. Such a case may be watched closely without immediate treatment, particularly if the patient does not have symptoms, because the speed with which the retinoschisis extended thus far is uncertain. Fundus photographs, in addition to the drawing and visual fields, are helpful in follow-up. If the retinoschisis progresses, treatment should be considered.

The presence of a break or breaks in an outer layer or in both the outer and the inner layers without significant retinal detachment may be handled the same way as full-thickness retinal break(s) without retinal detachment. Some breaks will develop extensive retinal detachment, impairing vision, and others will not. An outer layer break alone rarely causes full-thickness retinal detachment, particularly if the break is round and trophic in nature, even though it can be large or multiple. Retinal detachment can be limited within the area of retinoschisis; this is actually a detachment of the outer layer of retinoschisis from the pigment epithelium (Figs 181.10 and 181.11).[7, 15] Byer called this condition schisis detachment,[15] which can be followed-up without treatment.[19, 21] Clements and associates treated 52 patients with outer layer breaks without retinal detachment prophylactically. Six patients developed a retinal detachment. These authors believe that applying cryopexy to the outer layer breaks without retinal detachment should be avoided.[23] Full-thickness retinal detachment or a retinal detachment that extended outside the area of retinoschisis was observed in 16% of eyes with breaks only in an outer layer and in 77% of eyes with breaks in both layers.[21] Retinal detachment caused by an outer layer break or breaksalone is usually located near the break within the area of retinoschisis and spreads slightly beyond the retinoschisis, thus creating detachment of the full-thickness retina. The retinal detachment is usually shallow and remains localized (Fig. 181.12).

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FIGURE 181.10  Fundus drawing of a retinal detachment with three outer layer breaks. The detachment is limited to the area affected by the retinoschisis.

 

 

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FIGURE 181.11  Fundus drawing of a retinal detachment with six breaks formed in the outer layer of the retinoschisis. The detachment is limited to the area affected by retinoschisis.
From Schepens CL: Retinal detachment and allied diseases. Philadelphia: WB Saunders; 1983:560.

 

 

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FIGURE 181.12  Fundus photograph of a full-thickness retinal detachment in the posterior pole caused by outer layer breaks (arrows). The posterior edge of the breaks is not entirely clear. The outer layer in the area located anterior to the breaks is still attached to the pigment epithelium and has a fish-egg appearance (asterisk).

 

 

A retinal detachment caused by breaks in both the outer and the inner layers of retinoschisis often becomes extensive, sometimes total (Fig. 181.13). Therefore, retinoschisis with breaks in both layers without retinal detachment deserves more close follow-up than does one involving an outer layer break alone. When breaks are present in both layers of retinoschisis, multiple superotemporal and posterior inner layer breaks are accompanied by retinal detachment more frequently than one or a few inner layer breaks located nasally inferiorly and anteriorly (Table 181.2 and Fig. 181.14). Multiple outer layer breaks combined with inner layer breaks tend to develop retinal detachment more frequently than does a single outer layer break (Table 181.3). Size, location, and number of breaks; presence or absence of a full-thickness break outside the retinoschisis; and whether or not the retinoschisis is progressive are factors taken into consideration in treatment to prevent retinal detachment. Furthermore, the presence of cataract may impair the fundus view. It would be better, therefore, if breaks were treated before cataract surgery. The status of the fellow eye and the patient's age and general medical condition may also be considered. When considering the treatment, one must always weigh the treatment risks against those of observation. It should also be remembered that the field defect produced by disruption of the retinal neural network cannot be improved by reattaching two disrupted retinal layers. Therefore, treatment is directed toward preventing further progression of retinoschisis or retinal detachment.

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FIGURE 181.13  Fundus drawing of a full-thickness retinal detachment caused by the breaks in the outer layer at the 6:00 and 2:30 o'clock meridians, with rolled edges and five small breaks (arrows) in the inner layer.

 

 


TABLE 181.2   -- Inner Layer Breaks and Detachments in 78 Eyes

Inner Layer Breaks

Detachment (%)

No Detachment (%)

Total (%)

Number

 

 

 

1

16 (67)

8 (33)

24 (100)

2-4

30 (75)

10 (25)

40 (100)

5 or more

14 (100)

0 (0)

14 (100)

Total

60

18

78

Location

 

 

 

Superonasal

1 (33)

2 (67)

3 (100)

Superotemporal

37 (84)

7 (16)

44 (100)

Inferotemporal

22 (71)

9 (29)

31 (100)

Inferonasal

0 (0)

0 (0)

0

Total

60

18

78

Ora-equator

22 (67)

11 (33)

33 (100)

Equator-midway

37 (84)

7 (16)

44 (100)

Midway--posterior pole

1 (100)

0 (0)

1 (100)

Total

60

18

78

 

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FIGURE 181.14  When breaks in both layers of the retinoschisis are located superiorly, they are prone to produce a full-thickness retinal detachment (top left and right). Inferiorly located breaks may not (bottom left and right).

 

 


TABLE 181.3   -- Outer Layer Breaks and Retinal Detachments in 78 Eyes

Outer Layer Breaks (n)

Detachment (%)

No Detachment (%)

Total (%)

1

27 (68)

13 (32)

40 (100)

2-4

26 (87)

4 (13)

30 (100)

5 or more

7 (88)

1 (12)

8 (100)

Total

60

18

78

 

There are two modes of treatment. The first is demarcation of the advancing edge of retinoschisis by photocoagulation or cryoapplications, or a combination of the two. This methodrequires destruction of the normal retina at the edge of the retinoschisis, which already may be far advanced at the time of treatment. Therefore, the treatment further increases the field defect. The second mode is an attempt to collapse the inner layer by applying photocoagulation[20] or cryotherapy,[24] or both, to the entire outer layer with or without drainage of fluid from the cavity of the retinoschisis. The theories behind this method are that because the cellular elements of the retina are responsible for secretion of fluid into the retinoschisis cavity, their destruction by photocoagulation or cryotherapy explains the collapse of the retinoschisis,[25] or that the diffusion barrier present at the retinal pigment epithelium level is disrupted by photocoagulation or cryotherapy, causing the fluid in the retinoschisis cavity to diffuse into the choroid.[26] In the past, treatment with strong xenon photocoagulation caused the formation of the outer layer break and subsequent retinal detachment.[20, 21] Mild, contiguously applied laser coagulation appears to be much safer. The fluid in the retinoschisis cavity is usually very thick, making its complete removal through one scleral perforation difficult. The inner layer collapses in the area of the perforation site as the fluid is drained, but the fluid tends to be trapped in the area of retinoschisis away from the perforation. However, it is not essential to remove every drop of schisis fluid; the fluid either is absorbed slowly or remains without increasing in volume after the treatment.

The full-thickness retinal detachment caused by a break or breaks in the outer layer without a break in the inner layer presents unique clinical features. The retinoschisis usually is highly elevated before the formation of the outer layer break, which generally consists of a tear at the edge of the retinoschisis (Fig. 181.15) or multiple circular trophic holes (see Fig. 181.12). The break can be seen easily if it is a tear with an edge that may be rolled; it is sometimes difficult to detect because the contrast between the bare pigment epithelium and the attached outer layer can be poor. It is often impossible to detect the posterior edge of a break that leads to a full-thickness retinal detachment (see Fig. 181.12). The retinal detachment is usually shallow and often involves the macula (see Fig. 181.12). Five such cases in which the treatment was successful were described by Sulonen and co-workers.[27] If the outer layer surrounding the tear is still attached or is only slightly elevated from the pigment epithelium, laser photocoagulation or cryotherapy, or both, applied around the outer layer break may effectively close it, resulting in the spontaneous reattachment of the full-thickness retina (Fig. 181.16). Schwarze and Laqua also reported two similar cases in which they successfully demarcated the large outer layer breaks with argon laser.[28] Ambler and colleagues reported success in one of three patients.[22] They believed that weak laser coagulation was a reason for the failure in two cases.[22] This treatment is least invasive, but it will not work incases in which the outer layer is lifted at the edge of the break, and as a result, a good reaction to the laser treatment cannot be obtained. Even if the laser could seal off the outer layer break, the treatment probably will not prevent a new break from forming, with possible subsequent recurrent retinal detachment because the retinoschisis remains highly elevated.[22] The scleral buckling procedure, whereby the buckle is applied to close the outer layer break with drainage of subretinal fluid and fluid from the retinoschisis cavity through the perforation made from the sclera and choroid, results in retinal reattachment and almost complete collapse of the retinoschisis (Fig. 181.17). The perforation for fluid drainage is made through the existing break in the outer layer. The outer layer break can be large and is often located posteriorly. The application of a large buckle posteriorly tends to form the retinal fold and distort the macula, and the surgery can be quite invasive.

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FIGURE 181.15  Fundus drawing of a ballooning retinoschisis with a large outer break with rolled edges causing a shallow full-thickness retinal detachment posteriorly.
From Schepens CL: Retinal Detachment and Allied Diseases, vol 2. Philadelphia, WB Saunders, 1983, p 560.

 

 

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FIGURE 181.16  Fundus drawing of the same eye as in Figure 181.15 shows the area around the outer layer break before photocoagulation and cryoapplication (top left). After treatment, the full-thickness retinal detachment resolved. The retinoschisis remains the same (top right). Visual fields before (left) and after (right) treatment are shown at the bottom.

 

 

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FIGURE 181.17  Fundus drawing of an eye with retinoschisis (top left). Several months later, the same eye developed a large outer layer break at the posterior edge of the retinoschisis, causing a full-thickness retinal detachment posteriorly (top middle). After scleral buckling, the retina was reattached. A small pocket of fluid in the retinoschisis cavity remained in the periphery on the buckle (top right). Visual fields on each occasion are shown at the bottom.

 

 

The better approach is to ablate the entire outer layer with laser coagulation alone or a combination of laser and cryotherapy and drain the fluid and the subretinal space.[22] One such case is shown in Figures 181.18 to 181.21. The patient was a 54-year-old man with a 2-month history of visual disturbance in his left eye. The best-corrected vision was 20/70. The fundus of the left eye had extensive retinoschisis in the entire inferotemporal quadrant (Fig. 181.18). The break in theouter layer (Fig. 181.18) was located on the posterior edge of the retinoschisis in the area of the inferior major arcade of vessels. A shallow retinal detachment was observed posterior to the break involving the macula. The outer layer break was not easily recognizable (Fig. 181.19). Only the anterior edge of the break was visible; the posterior edge was not. It was also nearly impossible to determine where the retinoschisis ended and the full-thickness retinal detachment began. The white laser coagulation marks on the attached outer layer delineated the anterior edge of the outer layer break (Fig. 181.20). The laser applied directly to the outer layer break did not whiten because only the bare pigment epithelium was exposed. The entire area of retinoschisis was treated contiguously with laser coagulation except in the periphery, where cryotherapy was applied because of the easy accessibility of the peripheral retina by cryoprobe (Fig. 181.21). After the treatment, the retinoschisis collapsed and the retina reattached. The vision improved to 20/40, and the fundus was stable without signs of retinoschisis for 10 years after treatment.

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FIGURE 181.18  Fundus drawing of the retinoschisis with an outer layer break (arrows) and a full-thickness retinal detachment in the posterior pole. No inner layer break is seen. The outer layer of retinoschisis, which is not detached from the pigment epithelium, has a fish-egg appearance.

 

 

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FIGURE 181.19  Fundus photograph of the area of the outer layer break in the same eye as seen in Figure 181.18. The arrows indicate the anterior edge of the break.

 

 

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FIGURE 181.20  Fundus photograph of the same area as seen in Figure 181.19 immediately after photocoagulation. The anterior edge of the outer layer is well delineated by the photocoagulation scars.

 

 

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FIGURE 181.21  Top, Fundus drawing shows the areas treated with photocoagulation (small black circles) and with cryopexy (large black circles). The retina is detached posteriorly. The visual field is shown at the bottom.

 

 

Another treatment approach was introduced in 1990[29]; i.e., pars plana vitrectomy followed by internal drainage of subretinal and retinoschisis fluid through the intentional break created in the inner layer. As the fluid is drained internally, the gas is injected into the vitreous. The results appeared encouraging except for cataract formation or advancement, which often results after uncomplicated closed vitrectomy. The retinal detachment caused by the breaks in both the outer and the inner layers can become quite extensive (see Fig. 181.13) or total, obviously because of the free communication between the vitreous cavity and the subretinal space through the breaks in both layers of retinoschisis (see Fig. 181.6). The goal of treatment in such cases is to reattach the retina by closing all outer layer breaks, which may be difficult to recognize because only a portion of the break may be visible. The scleral buckling procedure is usually effective in closing the outer layer breaks. A full-thickness retinal break may coexist and should also be closed. When the entire edge of the outer layer break is not well visualized, the surgeon must determine the size and contour of the break from the visible portion and ascertain that the buckle is large enough to be effective. If the initial scleral buckling procedure fails and the retina again becomes detached, or if the retina temporarily attaches but becomes detached later, it is usually difficult to fid the original outer layer break postoperatively. As long as one detects and surgically closes all the breaks in the outer layer and the full-thickness retina, the results are relatively favorable.[30]

Several cases of retinal detachment were treated by cryopexy with simultaneous external subretinal fluid drainage and intraocular gas injection without a buckling procedure, which also led to favorable results.[19] More recently, progressive acquired retinoschisis without full-thickness retinal detachment and those associated with retinal detachment have been treated by closed vitrectomy and the use of a heavy liquid with or without a scleral buckling procedure.[14]

After vitrectomy and removal of the posterior hyaloid that strongly adhered to the inner layer, perfluorocarbon liquid was injected over the disk and the macula. The heavy liquid squeezed the usually thick, tenacious subretinal fluid and the fluid in the schisis cavity into the vitreous through the existing outer layer and inner layer hole or holes, reattached the retina, and flattened the retinoschisis.[14] The difficulty of the scleral approach in draining the fluid in the retinoschisis cavity was mentioned previously. Internal drainage of the fluid from the schisis cavity through a soft-tipped Teflon tube can also be difficult. Removal of the fluid usually requires relatively high suction on the tube, the tip of which is inserted into the schisis cavity through the inner layer break, and often an intentional break is enlarged sufficiently to allow insertion of the tube through it. The inner layer collapses near the tip of the suction tube as the thick fluid is drained out of the tube, but the other area of schisis remains elevated, making the complete collapse of the inner layer very difficult. Furthermore, unintentional but often unavoidable rubbing of the outer layer by the tip of the extrusion needle causes tearing of the fragile outer layer, further complicating the situation. The heavy liquid applied over the posterior pole in four cases by Lomeo and associates apparently squeezed the subretinal fluid along with the fluid in the retinoschisis into the vitreous cavity through the breaks, making the detached retina and elevated inner layer reattach.[14]

There are various methods of treating a retinal detachment associated with retinoschisis. Accumulation of more data from cases treated by different methods with long-term follow-up is needed to determine the best method in each case.

 

 

CONGENITAL RETINOSCHISIS

In congenital retinoschisis, retinal splitting usually occurs in the nerve fiber layer.[31] The disease is usually transmitted by an X-linked recessive trait and is nearly always found in males who are affected bilaterally, with the mother being an obligatory carrier. Rare cases of an autosomal type have been reported.[6, 32, 33] The retinal abnormality in these patients is probably present at birth; thus, it may be called congenital.[34] The disease affects whites, blacks,[34, 36] and Asians.[37] The prevalence is reported to be 1:1 5000 to 1:30000,[38] but the incidence appears to vary by region and country. A study of visually impaired children from four Nordic countries described the corresponding age- and sex-specific prevalence rates of X-linked retinoschisis (n = 1 million): 44.5 in Finland, 8.8 in Denmark, and 7.9 in Norway. No cases were reported from Iceland.[39] In this chapter, we describe the most common X-linked recessive type.

CLINICAL FEATURES

Because congenital retinoschisis frequently affects the macula or often causes vitreous hemorrhage, the initial symptoms are poor vision, strabismus, or nystagmus. Macular abnormalities are detected in virtually all cases[40, 41] and may be the only fundus fidings in congenital retinoschisis. The appearance ofthe macula varies. However, microcystic elevation or fie radiating folds from the fovea, or a combination of both, are most characteristic (Fig. 181.22).[34] Fluorescein angiography shows no dye leakage into these cystoid spaces, which is distinctly different from the microcystoid macular edema. In some cases, the retina is elevated extensively, occupying almost the entire posterior pole that is surrounded by the major vascular arcade (Fig. 181.23). The macular abnormality can be very subtle, with the superficial radiating fold barely detectable by careful slit-lamp examination. The use of red-free light usually helps detect the change (Fig. 181.22). In some cases, pigment mottling may be the only change, and in other cases, the absence of a foveal reflex is the only macular abnormality. Such fidings in the macula in the absence of the peripheral changes in old patients can be overlooked as a normal aging-related change. The macula may be displaced by vitreoretinal traction,[34] or it may have a punched-out lesion or thinning of the pigment epithelium and atrophy of the choriocapillaris, which may lead to a misdiagnosis of a congenital toxoplasmosis lesion. Central vision is impaired in most cases, and it usually varies from 20/40 to counting figers, but vision can be relatively good, even 20/20, in rare cases.[41]Very subtle changes in the macula with the absence of peripheral retinoschisis inchildren often lead to a diagnosis of amblyopia or strabismus instead of congenital retinoschisis, and these patients are followed up in the clinic as such. Four children were found to have congenital retinoschisis among 109 who had been diagnosed as having amblyopia.[42]

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FIGURE 181.22  Top, Fundus photograph of the macula in congenital retinoschisis shows a fine radiating fold from the fovea, which is more distinct in a monochromatic photograph (bottom).

 

 

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FIGURE 181.23  Fundus photograph of the posterior pole of congenital retinoschisis shows a huge, blister-like retinal elevation reaching the major vascular arcade.

 

 

Ophthalmoscopically visible peripheral retinoschisis is reported to occur in 71[41]-85%.[34] The most characteristic lesion outside of the macula is the ballooning elevation of the inner layer with a large oval hole or holes, usually in the lower fundus (Fig. 181.24). Occasionally, two separate areas of ballooning retinoschisis are observed in one eye.[34] Unlike acquired retinoschisis, which always originates from the ora serrata, the anterior border of congenital retinoschisis seldom extends to the ora serrata, and the posterior border of the congenital retinoschisis is usually convex.[34] Furthermore, in congenital retinoschisis, the inner layer breaks are larger and encountered more frequently than are the outer layer breaks, in contrast with acquired retinoschisis in which the opposite is true. This difference probably exists because the splitting occurs in the nerve fiber layers, the superficial layers of the retina in congenital retinoschisis,[31] as compared with acquired retinoschisis in which the splitting happens in the deeper retinal layer of the outer plexiform[8] or the inner nuclear[9] layers.

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FIGURE 181.24  Fundus drawing of congenital retinoschisis with large inner layer breaks.

 

 

The retinal blood vessels usually run in the inner layer or occasionally bridge the inner and outer layers. Sheathing of retinal vessels is seen in the area of retinoschisis.[34] In some cases, the inner layer is so elevated that it can be seen behind the lens on slit-lamp examination (Fig. 181.25). The inner layer holes can become quite large, almost as large as the retinoschisis itself, and the retinal vessels and the attached flimsy retinal tissue bridge these holes. In some cases, the inner layer is missing and the retinal vessels may float free in the vitreous cavity, a condition Mann and Macrae called a congenital vascular veil.[43] Retinal neovascularization may be seen on the surface of the inner layer schisis[34] as well as on the optic disk.[44] The neovascularization is also seen on the retina outside of the retinoschisis.[34] This neovascularization may lead to fibrous proliferation and traction retinal detachment, as in proliferative diabetic retinopathy, discussed later in this chapter. White, fie dendritic figures, probably of vascular origin, are often seen in the peripheral fundus, in which the inner layer is not highly elevated.

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FIGURE 181.25  Photograph of congenital retinoschisis with a highly elevated inner layer visible behind the lens.

 

 

Retinoschisis in the periphery may be indistinct and may be detected as a very low elevation of the inner layer only by viewing the fundus tangentially with a binocular indirect ophthalmoscope with scleral depression. Ophthalmoscopy without scleral depression often fails to detect very shallow retinoschisis in the periphery. Multiple small white dots usually more easily seen in shallow acquired retinoschisis on scleral depression are also observed in low-grade congenital retinoschisis. These white dots, which have been referred to as snowflakes,[34] are pale in color, not chalky white, and difficult to see against the pale fundus in white patients. These dots are more densely distributed than the white dots seen in retinitis punctata albescens. Different from the snowflakes, the fundus albipunctatus-like lesions have been reported in two Japanese patients with congenital retinoschisis.[45] The retina that does not appear elevated outside of the macula may have a patch of shiny reflex, which somewhat resembles wet silk.[40, 46, 47] The reflex may not be uniform and may have some blotchy patterns. The reflex, which is more readily visible when viewed by scleral depression, appears to originate from the retinal surface or the vitreoretinal interface. de Jong and coworkers described the gold-yellow reflex that disappears on light exposure (Mizuo-Nakamura phenomenon) in congenital retinoschisis.[48] These authors hypothesized that this phenomenon was caused by excess extracellular potassium in the retina that resulted from the decreased ability of the retinal Müller cells to scavenge for potassium.[48] Beside the vascular veil, which is actually the inner layer of the retinoschisis, translucent membranes without vessels are often seen floating free in the vitreous cavity, a part of the membrane attached to the inner layer or to the retina outside of the retinoschisis. The membrane may attach to the optic nerve or the macula, causing pseudopapillitis, dragging the retinal vessels near the disk, or causing macular displacement.[34] Nasal dragging of the retina may also be seen.[49] Hemorrhage, which can be the first symptom within the retinoschisis cavity or vitreous, is relatively common, and therates of occurrence range from 4-40%.[34, 41, 50] Vitreous hemorrhage may be the initial sign of the disease. In the late stage of congenital retinoschisis, the entire inner layer is missing, and the retinal vessels are invisible. The outer layer degenerates, and multiple pigment clumps appear (Fig. 181.26). Male patients with pigmentation and no visible retinal vessels in the lower half of the fundus should be suspected of having congenital retinoschisis until it is proved otherwise.

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FIGURE 181.26  Fundus photograph of advanced congenital retinoschisis shows extensive pigmentation and loss of retinal vessels in the inferior fundus.

 

 

Recently, optical coherence tomography (OCT) has become a useful tool in identifying patients with foveal retinoschisis. On OCT, the schisis cavities are seen as small cystoid spaces in the inner and mid retina with no concomitant retinal thickening. A classification system has been proposed using both visual acuity and OCT fidings.[51, 52] Ultrahigh-resolution OCT will bring more detailed anatomic information in patients with congenital retinoschisis.

The electroretinogram (ERG) in congenital retinoschisis is characteristic and diagnostic.[53] Because of the polymorphous fundus appearance in congenital retinoschisis, diagnosis based on the fundus examination may be difficult. In such a case, the ERG may help in the diagnosis. The ERG in congenital retinoschisis is characterized by a disproportional decrease of the b-wave amplitude compared with that of the a-wave. In the early stage of the disease or in mild cases, only a decrease of the b-wave amplitudes, along with the oscillatory potential and no change in the a-wave, is observed. The b:a wave amplitude ratio is especially reduced (Fig. 181.27b). Normal ERG tracings are shown in Figure 181.27a for comparison. This electroretinographic fiding is observed even in cases in which the visible fundus abnormality is limited to the macula. The ERG abnormality is found even in the patients whose visible abnormality detected only in the macula is extremely subtle and whose vision is 20/20. Because the ERG is a mass response, an abnormal ERG signifies that the retina outside the macula is diffusely affected, even in cases in which the visible abnormality is limited to the macula. When the disease progresses and the receptor degenerates, the a-wave amplitude also becomes smaller. However, the b-wave amplitude reduction is always greater; therefore, a low b:a wave amplitude ratio is always maintained (Fig. 181.27c). When the retinoschisis is far advanced and the fundus shows extensive pigment clumping, and when the retinal vessels are absent from the lower half or the more extended area of the fundus, the b-wave of the ERG may be entirely absent, leaving only a small a-wave or P III component (Fig. 181.27d).[54] With further disease progression, the a-wave also disappears, making the ERG completely nonrecordable. The focal macula ERG also shows a low b:a wave amplitude ratio with diminished oscillatory potentials.[55] In the cases in which the macular degeneration is advanced, the focal macular ERG becomes nonrecordable.[55]

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FIGURE 181.27  Electroretinogram (ERG) in congenital retinoschisis recorded with a relatively bright single flash of light under dark adaptation. (a) Normal ERG shows b:a wave amplitude ratio larger than 1 with good oscillatory potential. (b) ERG in an eye with only the macula involved with no peripheral retinoschisis shows selective depression of the b-wave amplitude without depression of the a-wave. The oscillatory potential also is diminished. (c) ERG in an eye in which the retina (both the macula and the periphery) is extensively involved shows that both the b- and the a-waves are depressed, but the b-wave depression is more prominent. (d) ERG in far-advanced retinoschisis. ERG shows only a small negative wave (a-wave) with complete loss of the b-wave.
(a-d) From Hirose T, Wolfe E, Hara A: Electrophysiological and psychophysical studies in congenital retinoschisis of X-linked recessive inheritance. Doc Ophthalmol Proc Ser 1977; 13:173, Kluwer Academic Publishers.

 

 

The clinical picture in the end-stage of congenital retinoschisis is not too different from that of retinitis pigmentosa: extensive pigmentation with narrow retinal vessels and a nonrecordable ERG with complete night blindness.[53] If the small a-wave is recordable with complete loss of the b-wave in the eye with pigmentary retinal degeneration, congenital retinoschisis should be suspected. The small b:a wave ratio in congenital retinoschisis indicates that the inner neural retinal layer is more involved than the receptor or Müller cells, which are impaired if we consider that the b-wave is generated by those cells.[56] A characteristic low ERG b:a wave amplitude ratio in congenital retinoschisis is not observed in acquired retinoschisis, in which the ERG is either normal or subnormal, depending on the extent of the area involved without preferential depression of the b-wave amplitude. This indicates that acquired retinoschisis is not a diffuse retinal degeneration like congenital retinoschisis. Dark adaptation,[53] the absolute thresholds for both rods and cones,[57] is only slightly impaired in the early stage of congenital retinoschisis or in a mild case when the ERG b-wave is already significantly depressed. This dissociation of electrophysiologic fidings and the psychophysical results were interpreted by Peachey and colleagues, who indicated that in congenital retinoschisis the pathologic condition starts with the Müller cells, whereas the sensory neural pathways are by and large operating with limited dysfunction, at least in the early stage of disease.[57]

Female heterozygote carriers usually have normal ophthal-moscopic and ERG fidings, but some abnormalities have been reported to show wrinkling of the internal limiting membrane around the fovea[58] or peripheral retinal alterations similar to those found in affected males,[59] peripheral retinal degeneration and gliosis.[60] The majority of these abnormalities, however, appear to be nonspecific and not consistent fidings. Because of the lack of detailed description of the peripheral retinoschisis found in a carrier,[59] it remains unclear whether this is consistent with congenital type or acquired, one which is commonly found in general populations.

The gene for congenital retinoschisis has been mapped to the distal short arm of the X-chromosome, specifically to Xp22.1-p22.2.[59, 61-67] Despite the variations in the ocular fundus in this disease, there is no evidence for genetic heterogeneity.[68] Numerous papers have been published that improved the resolution of the genetic map in the RS region. A study of Finnish patients reports that the critical region of RS could be narrowed to 0.2-0. 3 cM, between the markers DXS418 and HYAT1.[39] A DNA-based diagnosis appears to help identify heterozygous carriers of congenital retinoschisis and also serves in the early diagnosis of affected infants, along with ophthalmoscopic and electrophysiologic methods.[69, 70] More recently, the gene involved in congenital X-linked retinoschisis has been identified and mutation in this gene called XLRSI (X-linked retinoschisis I) was considered to cause congenital retinoschisis in males.[71] The gene has been screened for mutation that has been found to show enormous heterogeneity. However, regardless of the mutation type, congenital retinoschisis appeared to be caused by loss of function mutation only.[72]

In addition to genetic methods, psychophysical testing has been reported to be helpful in detecting heterozygous carriers. The method uses the impairment of the cone system to detect flicker as rods dark-adapt in normal individuals; conversely, if the dark-adapted rods are exposed to dim light, cone function improves. These normal rod-cone interactions are lacking in heterozygous carriers.[73]

 

 

HISTOLOGY

Studies of enucleated eyes with congenital retinoschisis show that the splitting occurs in the optic nerve fiber layers.[31] Periodic acid-Schiff-positive amorphous material is found in the retina. Ultrastructurally, the amorphous material consists of filaments measuring 11 nm in diameter. Condon and associates postulated that the intraretinal filaments are produced by defective Müller's cells and that their extracellular accumulation may lead to degeneration of these cells and subsequent schisis formation.[31] Kirsch and co-workers also found these filaments in the retina outside of the retinoschisis as well as in the retina affected by retinoschisis.[74] Histochemical study demonstrates that these filaments are of glial origin. Those authors also thought that defective Müller's cells produce glial fibrillary acidic protein and possibly S 100 protein, which accumulated within the retina and secondarily resulted in degeneration of these cells and schisis formation.[74]

An animal model of congenital retinoschisis has been created in Norrie's disease mutant mice by gene targeting technology.[75] The hemizygous and homozygous mice show retinoschisis ophthalmoscopically, with the former having a negative-type ERG.

 

 

MANAGEMENT

Congenital retinoschisis is typically stable, and slow progression may alternate with spontaneous remission or collapsing of retinoschisis. Spontaneous collapse of ballooning retinoschisis has been reported to occur in 2 weeks,[76] but such a rapid regression is very rare. Rapid progression of the disease is likely to occur during the first decade of life. By age 20 years, most cases, with few exceptions, stabilize in terms of the size of the retinoschisis.[35] Management of congenital retinoschisis requires careful fundus examination with binocular indirect ophthalmoscopy, scleral depression, and a large fundus drawing. Examination under general anesthesia is often necessary for infants and small children. Visual-field plotting is important but often unsatisfactory in the case of infants or young children. Patients are examined at intervals of every 3 months to 1 year, and at least once a year as long as no new signs and symptoms appear.

Because of the nonprogressive nature of congenital retinoschisis in most patients, no treatment is indicated unless complications arise that impair or threaten vision. Attempting to collapse the retinoschisis with photocoagulation is an unsatisfactory approach because of frequent complications of new break formation in the outer layer followed by retinal detachment.[52, 77, 78] However, panretinal photocoagulation was used successfully for disk neovascularization.[46] A fresh vitreous hemorrhage is best treated conservatively with bedrest alone and the use of bilateral patches. If the vitreous clears, the possible source of bleeding should be sought. Sources of vitreous hemorrhage may be neovascular tufts or stretched retinal vessels crossing a large inner layer break or those bridging the inner and outer layers. Closing the offending vessels with laser should be attempted when there is a recurrence of vitreous hemorrhage. If the vitreous does not clear within 1 week, it is often impractical to continue bed rest. The child may return to normal activity, including attending school, but must avoid vigorous physical exercise and be followed up with periodic examinations. The vitreous usually clears within several months after a vitreous hemorrhage. Vitrectomy is rarely necessary in eyes with significant vitreous hemorrhage in congenital retinoschisis. However, persistent chronic vitreous hemorrhage may be an exception, particularly when the other eye is already blind. Regillo and associates reported such a case in which a successful vitrectomy was performed.[79]

Retinal detachment had been considered a relatively rare complication in congenital retinoschisis.[42] However, it does occur and is not entirely rare in patients in whom the vitreoretinal pathologic condition is extensive. In one family, three boys who were affected with congenital retinoschisis all developed retinal detachment. The incidence of retinal detachment was reported to range from 11% to 22%.[35, 42, 51]

Three types of retinal detachment are found in eyes with congenital retinoschisis. The first is retinal detachment caused by breaks in both layers of retinoschisis (Fig. 181.28). The second type is caused by a full-thickness retinal break that develops outside the retinoschisis; this type of retinal detachment does not appear to be related directly to the retinoschisis, but the formation of the full-thickness retinal break may be related to the vitreoretinal pathologic condition involved in the eye with retinoschisis. The third type is a traction retinal detachment, which is similar to that of proliferative diabetic retinopathy in its fundus appearance and probably also in its mechanism of detachment; i.e., the fibrovascular proliferative tissues grow in front of the disk, contract, and detach the retina (Fig. 181.29). The retinal detachment thus created resembled a tabletop detachment, with the highest retinal elevation at its point of adhesion to the fibrovascular membrane. Detachment of the retina becomes shallow in the periphery. The retina may stay attached in the extreme periphery. The full-thickness retinal detachment caused by an outer layer break alone without a break in the inner layer seen in acquired retinoschisis has not been observed in congenital retinoschisis. The goal of treatment in retinal detachment is to close all outer layer and full-thickness breaks. In traction retinal detachment, vitrectomy is performed to reattach the retina.

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FIGURE 181.28  Fundus drawing of congenital retinoschisis with breaks in the inner (large black arrows) and the outer layers (small black arrow), causing a full-thickness retinal detachment. Schema of cross-section through the horizontal line (white arrow) is also shown.

 

 

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FIGURE 181.29  Fundus drawing of a traction retinal detachment in congenital retinoschisis with fibrovascular tissues from the disc. A large inner layer break is present (large arrow), but there is no outer layer break. Blood in the vitreous (small arrows) and the dendritic figures characteristic of congenital retinoschisis are seen at the 6:00 and 8:30 clock hour meridians (asterisks). Schema of the cross-section through the vertical line (white arrows) is also shown.

 

 

Regillo and associates reported surgical results in six cases that developed complications: three with rhegmatogenous retinal detachment, one with exudative retinal detachment, and two with vitreous hemorrhage. A scleral buckle was used to treat the retinal detachments, and vitrectomies were performed to treat vitreous hemorrhage and proliferative vitreoretinopathy that developed when the retina redetached. The fial results were favorable, but reoperations were required (average 1.8 surgeries).[79] The surgical results are reasonably favorable considering the complexity of this type of retinal detachment. A more radical surgical approach, i.e., removing the inner layer of retinoschisis, was performed by Trese and Ferrone.[80] The cases included those with overhanging inner layer retinoschises with blood in the schisis cavity blocking the macula without retinal detachment, and those with a traction detachment in the macula. These authors reported favorable results. However, the indications for removing the inner layer remain to be determined, particularly in cases of ballooning retinoschisis covering the macula without the presence of a retinal detachment. In such cases, further observation is an alternative because blood-containing bullous retinoschises can collapse spontaneously.[81] If there is no sign of spontaneous collapse during the observation period, surgically draining the fluid from the retinoschisis cavity from the scleral side with the intravitreous injection of air for the eye that does not have an inner layer break can lift the overhanging retinoschisis from the macula. Congenital retinoschisis confied to the macula has never been an indication for treatment. However, Azzolini and colleagues reported a case in which the surgery resulted in resolution of the macular schisis with good recovery of vision.[82] Retinoschisis itself rarely leads to total blindness. The prognosis of uncomplicated cases of congenital retinoschisis is generally not poor;[81] however, some cases develop diffuse pigmentation, narrowing retinal arteries, and total night blindness with nonrecordable ERGs as in retinitis pigmentosa.[53] Comparisons of clinical features between acquired and congenital retinoschisis are listed in Table 181.4.


TABLE 181.4   -- Comparison Between Acquired and Congenital Retinoschisis

Characteristic

Acquired

Congenital

Location of splitting in the retina

Outer plexiform layer or inner nuclear layer

Nerve fiber layer

Age

Usually over 50 yr

Usually 1-5 yr

Bilaterally

Very common (75-90%)

Virtually always (98%)

Hereditary

Occurs without heredity; rarely autosomal recessive or incomplete dominance

X-linked recessive; rarely autosomal

Subjective complaints

Rarely present in early stage

Poor vision, strabismus, nystagmus

Macula

Rarely affected

Usually affected, characteristic

Location of retinoschisis

Most commonly inferotemporal, contiguous to ora serrata

Inferior half, anterior edge located posterior to ora serrata

Breaks

Outer layer breaks large, more frequent (25%) than inner layer breaks (16%)

Inner layer breaks large and more frequent (44%) than outer layer breaks (16%)

Vitreous membranes

Usually absent

Common (50%)

Vitreous hemorrhage

Rare

Common (40%)

Retinal detachment

Rhegmatogenous

Rhegmatogenous or traction

Associated with other anomalies

None

Filtration angle anomalies, night blindness; negative (?) type electroretinogram

Attempt to collapse retinoschisis

Often successful

Usually unsuccessful and controversial

 

 

 

GOLDMANN-FAVRE DISEASE

One special type of congenital retinoschisis is Goldmann-Favre disease. It is a syndrome that consists of congenitalretinoschisis indistinguishable ophthalmoscopically from the X-linked recessive type with pigmentation in the fundus, complete night blindness, or loss of the scotopic b-wave of the ERG.[83, 84] The disease is transmitted by autosomal recessive inheritance. Favre reported two young patients who had this condition.[84] A more recent case has also been reported.[85] Because the disease affects the vitreous, retina, and retinal pigment epithelium, it is also called vitreotapetoretinal degeneration.[86]

The fundus appearance of congenital retinoschisis of X-linked recessive inheritance is polymorphous and complex. Because Goldmann-Favre disease apparently affects the retinal pigment epithelium in its early stage, in addition to the presence of the congenital retinoschisis, the clinical fidings of this disease are complex and sometimes misleading. Diffuse pigmentary retinal degeneration associated with rhegmatogenous retinal detachment[87] or a macular cyst[88] with no congenital retinoschisis should not be mistaken for Goldmann-Favre disease. The absence of typical peripheral retinoschisis makes diagnosing Goldmann-Favre disease more difficult because the visible abnormality in the fundus is limited to the macula, which may not show any characteristic fidings of retinoschisis. Fundus fidings in Goldmann-Favre disease probably vary depending on the severity and stage of the disease just as in X-linked retinoschisis.

The electrophysiologic tests, particularly the ERG and the electrooculogram (EOG), are helpful in diagnosis. Although the original two case reports of this disease describe nonrecordable ERGs, stimulus light used at that time was weak, just enough to elicit the scotopic b-wave for normal individuals. With stronger stimulus light, the ERG is recordable in patients with Goldmann-Favre disease. It is characterized by reduction of both the b- and the a-waves, but the reduction of the b-wave is more prominent than that of the a-wave, so that the b:a wave amplitude ratio is reduced, similar to the ERG in X-linked retinoschisis. Besides the decrease of the a-wave amplitude, its implicit time is prolonged in all cases, as is that of the b-wave. As a result, the ERG recorded with bright stimulus light shows a peculiar shape with small a- and b-waves, the latter more depressed than the former and the bottom of the a-wave having a round appearance rather than the normal spiky or pointed trough.[89] Furthermore, the ERG recorded under light adaptation does not differ greatly from that recorded in dark adaptation in Goldmann-Favre disease.[90] The EOG is abnormal in Goldmann-Favre disease.[89] The EOG in congenital retinoschisis with X-linked recessive inheritance is normal and becomes abnormal only in a very advanced stage of disease.[53] Difficulty in diagnosing the disease from the fundus fidings has already been mentioned. A fundus appearance described as "a new clinical entity" and called enhanced S cone syndrome resembles that of Goldmann-Favre disease.[91, 92] There is a unique electrophysiologic feature in the enhanced S cone syndrome, whereby the ERG recorded with bright white stimulus flash under light adaptation is not different from that obtained with dark adaptation despite greatly reduced 30-Hz flicker responses. Furthermore, there is an enhanced b-wave recorded with blue stimulation. These unique ERG fidings are observed in patients with Goldmann-Favre disease.[93] Kellner and Foerster reported five patients with enhanced blue-cone sensitivity along with maculopathy and peripheral retinoschisis with autosomal recessive inheritance who probably had Goldmann-Favre disease.[94] Whether the enhanced S cone syndrome is nothing but a new ERG fiding in Goldmann-Favre disease or whether it includes wider clinical entities than Goldmann-Favre disease is not known at this time.

No treatment is known to be effective in Goldmann-Favre disease, but Garweg and associates treated two patients using cyclosporine and bromocriptine. They hypothesized that this disease is a manifestation of a humoral and cellular immune response. As a result of cyclosporine treatment, the authors reported regression of the macular edema and flattening of the retinoschisis with subsequent improvement of vision.[95]

 

 

SECONDARY RETINOSCHISIS

Splitting neural layers of the retina or retinoschisis can be found in association with specific disease. In such cases, the retinoschisis is usually considered a complication of the original diseases, although cause-and-result relationships between the two or a mechanism by which the retinoschisis develops is not entirely clear in some cases. Conditions in which retinoschisis may develop include proliferative diabetic retinopathy,[7] regressed retinopathy of prematurity,[7] sickle-cell retinopathy,[96] occlusive vascular diseases, aplastic anemia,[97] peripheral uveitis,[98] trauma,[99] tumors, phakomatoses,[100] long-standing retinal detachment (retinal cyst), optic pit,[101] and Goodpasture's syndrome.[102] Although retinoschisis develops in the eyes afflicted with these conditions, a retinal detachment may also occur. In such a situation, it is often difficult to make a distinction between retinoschisis and long-standing retinal detachment when one is confronted with each clinical case. For instance, one often sees the peripheral retina elevated in young adults with regressed retinopathy of prematurity. The elevated retina shows signs of vitreoretinal traction or a break(s). Occasionally, two adjacent retinal vessels are pulled into the vitreous with the thin retina attached to them, but there is a defect or a large break in the retina bridging these two vessels. Pigmentation is often seen in the attached retina or slightly detached at the edge and on both sides of the retinal elevation, sometimes associated with subretinal exudate. If the elevated retina is concave and does not undulate despite the presence of retinal break(s), it is probably retinoschisis rather than a detachment. Furthermore, if the elevation does not progress during the course of observation, despite the presence of a break, this retinal elevation may be retinoschisis rather than retinal detachment. Secondary retinoschisis in proliferative diabetic retinopathy is relatively common. Lincoff and co-workers diagnosed 85 cases of retinoschises and 115 cases of traction retinal detachment among 200 cases of proliferative diabetic retinopathy with traction elevation of the retina.[103]

One peculiar type of retinoschisis is seen in conjunction with an optic pit that displays retinal elevation in the posterior pole.[101] The fiding that this elevation is retinoschisis rather than a sensory retinal detachment is appreciated by stereofundus photographs. The inner layers are transparent, and circumscribed detachment of the outer layers is seen through the inner layers. The outer layer detachment is round and does not communicate with the disc. The elevation of the inner layers is oval and much more extensive, communicating with the optic nerve pit. The same fidings are seen with optical coherence tomography.[104] This retinoschisis in the macula does not share the clinical features of retinoschisis elsewhere in the fundus in that it does not cause absolute scotoma and vision improves when the inner layer is flattened. Lincoff[101] speculated that this low elevation of the inner layer may not disrupt the neural network of the retina, but long, obliquely oriented Henle's fibers take a vertical course when the inner layer is elevated. A rare case of hemorrhage in the macular retinoschisis cavity with an optic nerve pit was reported.[105] Full-thickness retinal detachment limited to the posterior pole associated with an optic pit is usually treated successfully with contiguous laser coagulation applied to the retina next to the disk on the temporal side. Such treatment, however, is often unsuccessful for retinoschisis associated with an optic pit.[101, 104] Hoerauf and associates successfully treated two cases with retinoschisis associated with an optic pit by vitrectomy that included removal of the posterior hyaloid and gas tamponade.[106]

Retinoschisis is also noted in battered babies who show no evidence of ocular trauma. The fundus shows blood-filled retinal cysts that are often large and multiple and concentrated in the posterior pole.[99]The splitting of the neural retinal layer is considered to occur as a result of violent shaking (shaken baby syndrome). Subsequently, the blood migrates from the retina into the vitreous, leaving a retinal scar and markedly narrow retinal arteries. The selective reduction of the ERG b-wave amplitude with good preservation of the a-wave clearly indicates impairment of the diffuse lesions in the neural retinal layer. Autopsy fidings demonstrated multiple hemorrhages in the inner retina and in the preretinal, intrachoroidal, and intrascleral spaces in the area of the circle of Zinn-Haller.[107]

 

 

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