Hospital for Sick Children's, The: Atlas of Pediatric Ophthalmology & Strabismus, 1st Edition


Retina and Vitreous

Elise Héon

Nasrin Najm-Tehrani

Brenda Gallie

Wai-Ching Lam

Peter Kertes

Robert Devenyi

Carol Westall

Thomas W. Wilson

Alex V

The retina develops from the neuroectodermal cells of the optic cup around 4 weeks of gestation. Retinal development occurs in parallel with the development of other organ systems and therefore, explains why retinal diseases of childhood are often associated with disorders of the ear, kidney, or central nervous system. Primary care providers should be informed of the possibility of an underlying syndrome in all children with retinal disease. The retina matures from the center to the periphery.

The photoreceptors, essential to the processing of light, start to develop between 4 and 12 weeks of gestational age. The macula becomes recognizable between 24 and 26 weeks and the fovea will continue to mature after birth until 4 years of age. The retina is a fragile multilayered tissue where light is processed. The major step in the processing of light is called phototransduction, which takes place in the photoreceptors. The integrity of a photoreceptor requires a healthy surrounding, including the retinal pigmented epithelium (RPE) and inner sensory retina. Anomalies at any of these levels may lead to photoreceptor dysfunction and visual loss. This is usually the basis of the complex field of retinal dystrophies. Likewise, abnormalities of the choroid, the vasculature of which nourishes the outer retina, may also lead to retinal degener- ation. For most retinal and choroidal dystrophies, there is no treatment available, but this will change with the great influx of genetic knowledge about these conditions and the rapid progress of retinal gene and pharmacologic therapy.

Retinopathy of prematurity (ROP) is a potentially blinding disease affecting the retinal vessels in premature babies. It is characterized by arrest of the normal process of retinal vessel growth with resultant arteriovenous shunts and development of abnormal new vessels that may eventually lead to tractional retinal detachment and blindness. The disease is detected through a screening program for premature babies who are at risk and involves regular examination of the retina. The guidelines for inclusion in screening programs vary slightly between countries depending on local variations in incidence of ROP and neonatal care, but the infants at highest risk are those of low gestational age (<32 weeks) and low birth weight (<1,500 g). In these infants screening for ROP should start at 4 to 6 weeks after birth and continue at regular intervals until retinal vascularization has reached the temporal periphery (zone 3). The use of wide angle digital imaging has greatly improved our ability to observe and record the course of retinal maturation and document progression of disease, which allows for comparison between patient examinations and better communication between ophthalmologists and other health care providers. Fortunately, in the majority of cases ROP regresses spontaneously; however, in a small percentage the disease will progress with development of severe stages of ROP, with major visual consequences.

Retinoblastoma is the most common malignant tumor of childhood, but it is quite rare at an incidence of 1 in 15,000 live births. Retinoblastoma can be hereditary or nonhereditary. If left untreated, it can be fatal. For retinoblastoma and ROP, one must remember that the earliest diagnosis will produce the most favorable outcome.



Figure 8.1 Macular Hypoplasia

Macular hypoplasia can be seen as an isolated autosomal dominant or autosomal recessive disorder. It may also be seen in association with albinism, aniridia, or other developmental disorders of the eye. The hypoplasia is characterized by the absence of the usual reflection from the macular mound and a poorly developed fovea. Retinal vessels coursing through the central macula are common. In the absence of proper macular differentiation, the blood vessel pattern may not develop properly. Visual acuity is difficult to predict on the basis of macular appearance, but the presence of anomalous vessels that do not respect the horizontal meridian portends a worse prognosis.


Figure 8.2 Congenital Hypertrophy of the Retinal Pigmented Epithelium (CHRPE)

Congenital hypertrophy of the pigment epithelium may be isolated or associated with systemic disorders such as neurofibromatosis (seeChapter 23: Phakomatoses) or familial adenomatous polyposis (FAP). When FAP is associated with benign soft tissue and bony tumors, the condition is called Gardner syndrome. When brain tumors are present, the patient is said to have Turcot syndrome. FAP is associated with a very high risk for colonic cancer. Patients with more than two CHRPE lesions in one eye, bilateral CHRPE, or a family history of colon cancer should be screened with periodic colonoscopy starting in childhood. CHRPE lesions are usually asymptomatic unless the macula is involved. Lesions can be of various size and shape. They may have a hypopigmented ring (shown here) or a “tail.”


Figure 8.3 Bear Tracks

These congenital hyperpigmented areas of the retinal pigmented epithelium are clustered in a pattern that has similarity to the footprints of a bear. They tend to cluster in one quadrant, usually unilaterally, and increase in number and area covered from posterior to anterior. Unlike congenital hypertrophy of the pigment epithelium (Fig. 8.2), they are not associated with systemic disease and usually do not have hypopigmented edges or tails. There may be one or more clusters, each typically with a larger lesion surrounded by one or more smaller lesions.


Figure 8.4 Congenital Retinal Macrovessel

This rare benign vascular anomaly (arrow) is not associated with leakage or systemic disease (as might be seen in the capillary hemangioma of von Hippel-Lindau disease, Chapter 23: Phakomatoses, Fig. 23.12). Even though these vessels may appear in areas of retina not usually vascularized in this fashion, as shown here, unlike the anomalous vessels of macular hypoplasia (Fig. 8.1), congenital macrovessels are typically associated with normal retinal development and function.




Figure 8.5 Immature Retina

The retina is often not fully vascularized until 36 weeks gestation. The nasal retina vascularizes before the temporal periphery. In this premature child, the retinal vessels taper without clear demarcation of the peripheral avascular retina (asterisk). The choroidal vessels visible through the thin avascular retina are easily mistaken for retinal vessels by the inexperienced examiner. The macular area is featureless, the foveal reflex is blunted, and the fovea cannot be located easily. In this case, an arteriovenous loop is visible joining the superior temporal retinal arteriole to the venule (arrow). The extent of vascularization of the retina is just as far as the border of zone 1 and zone 2. According to the International Classification of Retinopathy of Prematurity, the zones of retinopathy of prematurity in the developing retina are as follows:

• Zone 1 is a circle centered on the optic disc, the radius of which is twice the distance between the disc and the fovea.

• Zone 2 is a circle centered on the optic disc, the radius of which is equal to the distance between the disc and the nasal ora.

• Zone 3 is the remaining crescent-shaped area bounded by the outer boundary of zone 2 and the ora serrata, the widest part of which is in the temporal retina. This crescent tapers as it approaches the nasal ora.


Figure 8.6 Stage 1 Retinopathy of Prematurity in Zone 2

These images demonstrate a demarcation line between vascularized and nonvascularized (asterisk) retina. The left image is that of a darkly pigmented fundus. The right image is that of a Caucasian infant. There is a “hold up” in the normal growth of the retinal vessels. The white line demarcating the extent of retinal vascularization is flat and thin. The vessels posterior to the demarcation line are dilated rather than tapered, and there is prominence of branching just behind the demarcation line. Although no treatment is indicated and the prognosis for resolution is excellent, careful follow-up, perhaps no later than 2 weeks, is required.




Figure 8.7 Stage 2 Retinopathy of Prematurity (ROP)

With progression of ROP the demarcation line will become elevated, gain volume, and form a ridge (arrow). The distinction between stage 1 and stage 2 is much better appreciated in a three-dimensional view of the retina, using scleral depression to look at the ridge in profile (i.e., tangentially). It may be more difficult to distinguish between stage 1 (Fig. 8.6) and 2 on two-dimensional imaging. Note the associated vascular changes including peripheral vessel dilation, tortuosity, and hyperacute branching. Also note the few peripapillary intraretinal hemorrhages as sometimes seen in active disease following examination.


Figure 8.8 Stage 3 Retinopathy of Prematurity—Mild

With further progression of disease, there is development of neovascularization within the extra-retinal proliferation. As a result, the extra-retinal proliferation changes color from white to pink and becomes broader. The neovascularization is above the plane of the retina and can extend posteriorly over the retinal surface or centrally into the vitreous. The extra-retinal proliferation can become more irregular in outline with development of neovascularization. There is notable vascular dilation and tortuosity close to the extra-retinal proliferation, which may extend posteriorly to the posterior pole. Stage 3 may be mild, moderate, or severe as defined by the number of clock hours and the degree of neovascularization. Hemorrhage can be seen here along the anterior border of the extra-retinal proliferation (arrow).


Figure 8.9 Stage 3 Retinopathy of Prematurity— Moderate

As stage 3 becomes more advanced, the neovascularization is more marked and the extra-retinal proliferation more pink in color. The retinal vessels are obscured as they lead up to the extra-retinal proliferation by the posterior extension of extraretinal (i.e., preretinal) neovascularization over the surface of the retina. Note also the increasing dilation and tortuosity of the retinal vessels.


Figure 8.10 Stage 3 Retinopathy of Prematurity (ROP)—Severe

This image shows severe stage 3 ROP as characterized by a broad neovascularized extraretinal ridge with a ragged posterior border with clearly visible popcorns (Fig. 8.12). There is hemorrhage along the anterior border of the ridge (arrow). The stage 3 ROP extended for 360 degrees (12 clock hours) in this baby. The retinal vessels in the posterior pole around the optic disc are clearly dilated and tortuous.




Figure 8.11 Stage 3 Retinopathy of Prematurity (ROP)—Severe

These images show high magnification of severe stage 3 ROP. In the left image the photographer has focused on the extraretinal neovascularization, which is above the plane of the retina: The retinal vessels leading up to the extra-retinal proliferation are not in focus. In the right image of the same area the photographer has focused on the retinal vessels behind the extra-retinal proliferation, and therefore the neovascular extra-retinal proliferation is out of focus. The white area anterior to the extra-retinal proliferation(asterisks) shows the near confluent diode laser treatment to the vascular retina.


Figure 8.12 “Popcorn” Retinopathy of Prematurity (ROP)

“Popcorn” ROP is a term used to refer to isolated clumps of new vessels posterior to the ridge. They are clearly seen to be on the surface of the retina and obscure the underlying retinal vessels. Development of “popcorn” may be seen in association with stage 2 ROP. The clumps may coalesce and eventually result in progression to stage 3. Popcorns can also occur later in the course of ROP and be associated with the regression phase and peripheral advancement of stage 2. In this image, the popcorns are seen posterior to an area of severe stage 3 associated with some bleeding along the neovascular extra-retinal proliferation. Near confluent laser treatment was applied to the avascular retina (appearing here as white areas, asterisk) and resulted in regression of the disease.


Figure 8.13 Stage 4a Retinopathy of Prematurity (ROP)

Following diode laser treatment in this eye with severe ROP, regression of the acute neovascular process was achieved. However, there is significant cicatricial change with resultant straightening of the temporal vascular arcades and temporal ectopia (“dragging”) of the fovea. In the more peripheral inferotemporal retina (bottom left section of image), the retina is elevated (and out of focus). Stage 4a ROP is defined by this partial retinal detachment not involving the macula. In this case, the retinal detachment improved spontaneously without any treatment.




Figure 8.14 Stage 4b Retinopathy of Prematurity (ROP)

In stage 4b ROP, the partial retinal detachment involves the macula. Note the significant cicatrization and temporal dragging of both temporal and nasal vessels and tractional retinal detachment, which has involved the fovea. The macular architecture is almost unrecognizable and the fovea can no longer be clearly identified. The visual prognosis for stage 4b ROP is very poor, with significant risk of progression to further retinal detachment over time without surgical intervention.


Figure 8.15 Stage 5 Retinopathy of Prematurity (ROP)

In stage 5 ROP, the retina is completely detached. Note the marked dilation of the retinal vessels and obscuration of the optic disc due to the funnel-shaped total retinal detachment. The retina has a glassy appearance. Progressive fibrosis will result in closure of the funnel over time. This degree of severity of disease is no longer amenable to laser treatment, and surgical treatment to release tractional retinal detachment by vitrectomy is often not successful. The visual prognosis is dismal.




Figure 8.16 Retinopathy of Prematurity (ROP)—Plus Disease

Plus disease is a feature that may or may not be present in cases of retinopathy of prematurity and is used to grade severity. This image shows posterior pole retinal vascular dilation and tortuosity in all four quadrants of the major vascular arcades around the optic disc. Development of plus disease in the course of progression of disease is a significant finding and portends a worse prognosis. When trying to determine if a patient has plus disease by photographic images, it is important to look at the retinal vasculature at the same level of magnification when comparing images.


Figure 8.17 Retinopathy of Prematurity (ROP)—Anterior Plus Disease

Severe plus disease in the posterior segment may be accompanied by iris vascular engorgement, poor pupillary dilation, and vitreous haze. The accompanying iris vessel engorgement and poor dilation of the pupil are particularly problematic in that not only do they herald development of severe retinopathy of prematurity, but they also prevent adequate visualization of the fundus for examination and performing treatment if needed. Although uncommon, spontaneous hyphema may also occur. In the absence of iris vascular engorgement, one should not make the diagnosis of plus disease based on poor pupillary dilation alone. Rather, improper or ineffective installation of mydriatics may be the cause.




Figure 8.18 Retinopathy of Prematurity (ROP)—Pre-plus Disease

With the usual recommended serial examinations, progression of the changes in the vessels around the optic disc may be observed over time. The degree of vascular dilation and tortuosity shown here is not severe enough to be labeled as plus disease (Fig. 8.16) but is greater than normal. There is mild dilation of the retinal venules and mild tortuosity of the retinal arterioles. The term pre-plus disease is used to describe this intermediate stage.


Figure 8.19 Aggressive Posterior Retinopathy of Prematurity (AP-ROP)

This less common form of ROP, also known as “rush” disease, is seen more frequently in the very-low-birth-weight and low-gestational-age babies. It is located in zone 1 or posterior zone 2 and is often rapidly progressive with prominence of plus disease (Fig. 8.16) and frequently progresses to stage 5 (Fig. 8.15) without treatment. It often does not progress through the classical stages 1 to 3 of ROP and may be associated with islands of avascular retina within the vascularized retina. In this image there is lack of clear evidence of ROP temporally yet severe stage 3 nasally. There is no clear white demarcation line temporally, but there is evidence of extension nasally of neovascularization into the vitreous that has resulted in blurring and a pink appearance of the ridge.




Figure 8.20 Zone 1 Retinopathy of Prematurity (ROP)

ROP is also graded by zones. One of the most severe forms of ROP includes presence of disease within zone 1, also known as rush disease (see Fig. 8.19). Zone 1 is an area subtended by a circle centered on the optic disc. The diameter of the circle is equal to twice the distance between the center of the optic disc and the fovea. In this image, avascular retina (note that choroidal vessels can still be seen under the avascular retina, asterisk) is visible within zone 1. The vessels of the superior and inferior temporal arcades are joined together in the form of an arteriovenous loop. Dilation and tortuosity of these vessels extend as far posteriorly as the optic disc.


Figure 8.21 Nasal–Temporal Asymmetry of Retinal Vascularization

These images, taken to show the extent of retinal vascularization nasally and temporally in the two eyes of an infant, can be compared to demonstrate this frequently observed phenomenon. Comparing the distance between the furthest extent of vascularization of the retina on the temporal and nasal sides of the optic disc, further progression of vascularization temporal to the disc is evident when compared with the retina on the nasal side of the optic disc.


Figure 8.22 Retinopathy of Prematurity Treatment

This image demonstrates moderate stage 3 disease (Fig. 8.9) that has been treated by diode laser to the avascular retina (multiple white areas on right side of image). A common problem is to “skip” areas (left image) of avascular retina, particularly in the trough between the neovascular ridge and the area of avascular retina brought into view by indentation. Photography of the treated retina at the end of the laser procedure can help to identify these skipped areas. Timely “fill-in” laser treatment to these areas will help result in resolution of active disease (right image).




Figure 8.23 Regressed Retinopathy of Prematurity (ROP)

ROP may also regress spontaneously. Regression occurs when the ridge resolves and vessels (arrow) cross into the former avascular retina. Pigmentary changes, as seen here, may also be observed. This regression can occur without retinal detachment or overlying vitreous change.


Figure 8.24 Retinal Dysplasia

Retinal dysplasia may occur as an isolated autosomal recessive X-linked disorder or in association with systemic findings. It most often appears as congenital nonattachment of the retina, as shown in this prenatal ultrasound (left image). This must be differentiated from congenital/infantile retinal detachment, where an otherwise normally differentiated retina is detached, for example, by traction or trauma. Walker-Warburg syndrome is also known as HARD +/- E: Hydrocephalus, agyria (i.e., lissencephaly, right image), retinal dysplasia +/- encephalocele (and/or Dandy-Walker malformation). Patients are usually severely developmentally delayed.




Figure 8.25 Walker-Warburg Syndrome

Affected patients may also have anterior segment dysgenesis with microphthalmia; cataract and glaucoma may be present, as shown here. Peters anomaly (Chapter 5: Cornea, Fig. 5.1) has also been observed. Differential diagnosis of retinal dysplasia includes Norrie disease. Any case of retinal nonattachment may have secondary changes in the anterior segment, in particular shallowing and closed angle glaucoma.


Figure 8.26 Norrie Disease

Norrie disease is an X-linked recessive disorder characterized by retinal dysplasia, hearing loss, developmental delay, and psychiatric disturbances in later childhood or young adulthood, but without developmental brain anomalies or anterior segment anomalies. The retina presents as nonattached in infancy, often leading to bilateral phthisis. Note the disorganized appearance of the dysplastic nonattached retina on this B-scan image. The gene that is mutated in this disorder, located at Xp11.4, may also play a role in X-linked recessive familial exudative vitreoretinopathy (Fig. 8.38) and Coats disease (Fig. 8.40).




Figure 27 Best Disease

Best disease, or vitelliform macular dystrophy, is an autosomal dominant macular dystrophy characterized by mutations in the Bestrophin gene (VMD2) located on chromosome 11. Best disease has great clinical variability between families and within families. The visual impairment depends on the localization and size of the retinal lesions. The electrooculogram is usually diagnostic with Arden ratio values usually below 1.5. The retinal lesions evolve through several stages, which can include a normal retina progressing to (A) RPE mottling or a yellow foveal dot, (B) the vitelliform stage (“egg yoke”), (C) the “scrambled egg” stage, (D) the pseudohypopyon stage, and finally (E) scar.


Figure 28 Stargardt Disease

Stargardt disease is an autosomal recessive maculopathy due to mutations in the ABCA4 gene located on chromosome 1. This is the most common form of macular degeneration in childhood. The phenotype variability can be quite broad at the level of fundus appearance and natural history. The maculopathy can present with or without pisciform flecks (A) and is usually relentlessly progressive. If there is foveal sparing the visual acuity can remain quite good. Most cases present with a phenotype in between these two images where the macula has a beaten metal appearance with some fleck deposits, not necessarily pisciform (B). The arteriovenous phase intravenous angiogram shows the typical choroidal silence, seen to some degree in 80% to 85% of cases (C).




Figure 29 Retinitis Pigmentosa

Retinitis pigmentosa is a genetically and clinically heterogeneous group of disorders for which over 50% of the involved genes have been identified. The disease is characterized by a progressive rod–cone dystrophy detected by electroretinogram recording over time, leading to night blindness and constricted visual field. The photoreceptor degeneration is accompanied by “bone spicule”–like pigmentation around the equator of the retina (A, age 39 years; B, age 50 years). Other signs include narrowing of retinal vessels (C, D, E) and developing pallor of the optic nerve. Some patients may show little pigmentation (D, E) but usually some degree of choriocapillaris atrophy or retinal pigmented epithelium dropout, specifically around the equator. Some atypical cases will present with very coarse pigmentation (E). Patients with retinitis pigmentosa may lose some central vision due to macular edema (F).




Figure 8.30 Retinitis Pigmentosa Sine Pigmento

Some cases of retinitis pigmentosa tend to only develop pigment very late in the course of the disease or not at all. It is not surprising to see an absence of pigment in children, which can be misleading if electrophysiology assessment is not available.


Figure 8.31 Unilateral Retinitis Pigmentosa

Unilateral retinitis pigmentosa is uncommon and should be considered acquired, for example, due to trauma or infection, until proven otherwise. In older individuals one must rule out a possible vascular ischemic cause, in particular due to decreased carotid flow ipsilateral to the affected eye. At all ages a viral, immunologic cause must also be ruled out.


Figure 8.32 Bardet-Biedl Syndrome

The cardinal features of the autosomal recessive Bardet-Biedl syndrome include retinal dystrophy, obesity, polydactyly, hypo- gonadism, learning disabilities, and kidney anomalies, among other features. The expression is variable between families and often within families. Multiple genes have been implicated, and oligogenic (e.g., triallelic) inheritance has also been proposed in some cases. There is usually no bone spicule pigmentation in the early stages of the disease. The retinopathy is more characterized by an equatorial depigmentation and mottling. There may be a geographic type of macular atrophy developing in the teenage years or adulthood. This patient shows a common finger shape with brachydactyly. This patient also had a sixth digit on the ulnar side that was removed (not shown).




Figure 33 Leber Congenital Amaurosis (LCA)

LCA is a congenital form or very-early-onset form of retinitis pigmentosa that leads to severe visual impairment. Nystagmus is usually present. The fundus appearance can be quite variable and normal looking in the earliest stages (A). Approximately 10% of cases will have a colobomalike lesion (B, E). The retinopathy usually shows a combination of “bone spicule”–like pigmentation, mottling, and marked retinal vascular attenuation (B, C). Not infrequently, the pigmentation can be coarser, mimicking “leopard spots” (D, E).


Figure 8.34 Juvenile X-linked Retinoschisis (XLRS)

Peripheral schisis may be isolated, posttraumatic, or a sign of XLRS. The schisis may progress to a retinal detachment. XLRS also usually shows a macular schisis, at least in the early stages, and a negative wave scotopic electroretinogram (a-wave greater than b-wave) in response to a standard bright flash. The gene XLRS1 has been cloned and is available for molecular testing.




Figure 8.35 Cone–Rod Dystrophy

Cone–rod dystrophies are characterized by a predominant dysfunction of the cones over the rods (cone system electroretinogram reduction greater than rod system). Usually the visual field deficit shows a central scotoma and the patient retains peripheral islands of visual. The diagnosis is made primarily on the basis of electrophysiology. Macular changes are usually present to a variable degree of severity (left image) and equatorial pigmentation eventually manifests (right image).


Figure 8.36 Gyrate Atrophy

Gyrate atrophy is an autosomal recessive retinal dystrophy due to a decrease in the enzymatic activity of ornithine amino transferase. This is usually an ocular condition only. The disease starts as discrete, round, atrophic patches of the retinal pigment epithelium and choroid that then coalesce to form the classic scalloped lesions (left image). The macula is spared until late. “Bone spicule”–like pigmentation may develop in the areas of atrophy (right image). As in other rod–cone dystrophies, posterior subcapsular cataracts can develop at an early age (Chapter 7: Lens, Fig. 7.12). An arginine-deficient diet may slow the progression of the disease.


Figure 37 Choroideremia

Choroideremia is an X-linked disorder affecting both rods and cones because of a defect in the REP1 gene. Molecular testing of the REP1 protein is available. In all cases the central visual acuity is well preserved until quite late in the course of the disease. The fundus of an 8-year-old boy with early choriocapillary atrophy with bone spicule pigmentation is shown (A). The choriocapillaris atrophy is more obvious on intravenous fluorescein angiography. The carrier female can be manifest to a variable degree, showing mild equatorial mottling (B) or more pigmentary changes (C). The late stage in affected males shows almost total choriocapillary atrophy with a minimal residual macular island (D).




Figure 38 Familial Exudative Vitreoretinopathy (FEVR)

FEVR is a genetically heterogeneous disorder of great variability in its clinical manifestation. It may be autosomal dominant or X-linked recessive. Two genes have been identified and are available for genetic testing (FZD4 and LRP5). It may mimic retinopathy of prematurity in a nonpremature child. The mild disease (A, B) shows dragging and straightening of the peripheral retinal vessels. The intravenous fluorescein angiography is very useful in establishing the diagnosis as it emphasizes the perfusion and vascular anomalies(C, D). There may be a peripheral avascular zone of retina with vascular incompetence, hemorrhage, and leakage at the edge of the vascularized retina. Treatment is conducted by laser or cryotherapy and is aimed at obliterating the avascular retina and incompetent vessels. Neovascularization and traction retinal detachment may also occur.


Figure 39 Pathologic High Myopia

High myopia may be isolated or syndromic. It may be sporadic or inherited. Isolated high myopia is often autosomal dominant. Typical changes include choroidal sclerosis (A), a staphyloma of the posterior pole, and peripapillary atrophy (B) with or without tilting of the disc. Severe myopia can also be associated with anomalies of the posterior pole such as vascular anomalies, hemorrhages (C), and lacquer cracks. One must always rule out any possibly associated connective tissue disorders such as Stickler or Marfan syndrome (seeChapter 28: Skeletal). High myopia itself can reduce electroretinogram amplitudes, and axial length must be taken into account in the analysis.




Figure 8.40 Coats Disease

Coats disease is a sporadic disorder characterized by a defect of retinal vascular development that results in vessel leakage, subretinal exudation, and retinal detachment. Coats disease is usually diagnosed in childhood because of unilateral decreased vision. The disease mostly affects males and shows vascular telangiectasis, lipid exudation, macular exudates, and areas of capillary nonperfusion with adjacent webs of filigree-like capillaries. Treatment includes laser photocoagulation, cryotherapy, and surgery, depending on the stage of the disease. Enucleation may be required for blind painful eyes that are candidates for other therapies. The left image shows typical yellow subretinal and intraretinal exudates encroaching on the fovea. The right image shows the retina anterior to the exudate with dilated telangiectatic vessels. These vessels leak proteins to give rise to the exudation. The vascular anomalies are sometimes referred to as “light bulbs.” (The authors are grateful for the contributions to this legend by Drs. Vikas Khetan and Zhao Jun Yang.)


Figure 8.41 Coats Disease—Intravenous Fluorescein Angiogram

Angiogram of the patient pictured in Fig. 8.40 shows dilated tortuous vessels, an area of ischemic retina, and arteriovenous shunts. Many arterioles end in macroaneurysm-like dilations surrounded by avascular areas or complete vascular closure. The pathogenesis of Coats disease may include arteriovenous shunts resulting in increased pressure on the veins (blue), causing them to become telangiectatic and leaky. Arrows indicate shunts. (The authors are grateful for the contributions to this legend by Drs. Vikas Khetan and Zhao Jun Yang.)




Figure 8.42 Retinoblastoma Group A

The International Intraocular Retinoblastoma Classification (IIRC) was recently designed to classify intraocular retinoblastoma and predict the most likely prognosis with the current primary treatments available. Chemotherapy has now largely replaced radiotherapy as the primary mode of treatment for retinoblastoma. This eye would be classified as IIRC Group A: All tumors ≤3 mm in maximum dimension and ≥3 mm from the fovea and ≥1.5 mm from the optic disc. The arrow indicates the early tumor, which was treated successfully with 532 nm laser. (The authors are grateful for the contributions to this legend by Drs. Vikas Khetan and Zhao Jun Yang.)


Figure 8.43 Retinoblastoma Group A

The arrows indicate the multiple tumors in the eyes of this patient with a germline mutation. Retinoblastoma tumors are a manifestation of the “two-hit” hypothesis, whereby a second genetic event is required on the allele not carrying the germline mutation in the RB gene, thus resulting in loss of heterozygosity. Alternatively, in the absence of a germline mutation, two mutational events can occur after fertilization in retinal cells. In this case, since all the tumors (arrows) are away from the fovea and optic nerve in this patient, laser photocoagulation would be the treatment of choice. The red arrow shows a tumor immediately following treatment with 532-nm laser. (The authors are grateful for the contributions to this legend by Drs. Vikas Khetan and Zhao Jun Yang.)


Figure 8.44 Retinoblastoma Group B

This eye would be classified as International Intraocular Retinoblastoma Classification Group B: Bilateral multifocal retinoblastoma, here occurring in a premature infant, compromising both macula and optic nerve. The hemorrhages seen on the tumor surface are in part related to vaginal birth. This infant was treated with stereotactic radiation to the posterior pole of both eyes, since focal therapy would be blinding and the liver and kidney function was not mature to allow for a full dose of chemotherapy.




Figure 8.45 Retinoblastoma Group C

Retinoblastoma may cause vitreous seeding (Group C). This eye would be classified as International Intraocular Retinoblastoma Classification Group C: Retinoblastoma with discrete vitreous seeding close to tumor. The tumor is too large to be managed with focal therapy alone and requires chemotherapy to shrink the tumor, followed by focal therapy (laser and/or cryotherapy). (The authors are grateful for the contributions to this legend by Drs. Vikas Khetan and Zhao Jun Yang.)


Figure 8.46 Retinoblastoma Group D

Retinoblastoma may present as total retinal detachment; shown here is an International Intraocular Retinoblastoma Classification Group D eye: Massive or diffuse with total exudative retinal detachment. There is a large tumor that may respond to chemotherapy using cyclosporine followed by carboplatin, vincristine, and VM26. Six or more cycles of chemotherapy and repeated focal therapy would be necessary. (The authors are grateful for the contributions to this legend by Drs. Vikas Khetan and Zhao Jun Yang.)


Figure 8.47 Retinoblastoma Group D

This eye would be classified as International Intraocular Retinoblastoma Classification Group D: Diffuse subretinal or vitreous seeding, present or past, may cause implanted retinoblastoma (arrow), which can be difficult to distinguish from new primary retinoblastoma. Management of such an eye requires chemotherapy followed by focal therapy. Cryotherapy to normal retina less than 48 hours prior to systemic chemotherapy can increase the concentration of carboplatin in the vitreous, particularly important for eyes with vitreous seeding. (The authors are grateful for the contributions to this legend by Drs. Vikas Khetan and Zhao Jun Yang.)




Figure 8.48 Retinoblastoma Group D

This eye is classified as International Intraocular Retinoblastoma Classification Group D: Retinoblastoma with massive or diffuse exudative retinal detachment. Chemotherapy is required to shrink the tumor, followed by focal therapy. Arrows show shallow detachment with subretinal tumor or exudate. Retinal detachments associated with active retinoblastoma usually resolve with a successful response to chemotherapy, as the main tumor mass also shrinks. (The authors are grateful for the contributions to this legend by Drs. Vikas Khetan and Zhao Jun Yang.)


Figure 8.49 Retinoblastoma Group E: Tumor Touching the Lens

This eye would be classified as International Intraocular Retinoblastoma Classification Group E: Retinoblastoma tumor touching the lens. The arrow in the right image shows the lens capsule. Such eyes are not effectively treated with chemotherapy and focal therapy, since residual tumor on the back of the lens cannot be treated with focal therapy. Group E eyes require enucleation, as advanced tumor has the potential for extraocular disease.




Figure 8.50 Retinoblastoma Group E: Neovascularization of the Iris

This eye would be classified as International Intraocular Retinoblastoma Classification Group E: Neovascular glaucoma. Neovascularization is evident with fine new vessels seen on the surface of the iris. An eye with retinoblastoma and neovascular glaucoma requires removal, since the potential for metastatic spread is increased. Elevated intraocular pressure also increases the risk that tumor has invaded the optic nerve past the lamina cribosa. Histopathologic assessment of the nerve and globe will determine the need for additional treatment. (The authors are grateful for the contributions to this legend by Drs. Vikas Khetan and Zhao Jun Yang.)


Figure 8.51 Retinoblastoma Group E: Optic Nerve Infiltration

Enucleation of an eye with increased intraocular pressure and suspicious imaging of the optic nerve on computed tomography scan and magnetic resonance imaging is important to establish the extent of disease. Following enucleation, histopathology in this eye reveals retinoblastoma infiltrating the optic nerve. This has a significant negative effect on survival prognosis. Chemotherapy may be required following enucleating if the margin is positive. These cases must be assessed with a lumbar puncture. Prophylactic chemotherapy and/or radiation may be required. (The authors are grateful for the contributions to this legend by Drs. Vikas Khetan and Zhao Jun Yang.)


Figure 8.52 Retinoblastoma Group E: Anterior Chamber Retinoblastoma

This eye would be classified as International Intraocular Retinoblastoma Classification Group E: Retinoblastoma with anterior chamber seeding. In addition to enucleation, children with such advanced disease require metastatic workup, including bone scan and regular bone marrow and lumbar puncture to determine the presence or absence of extraocular disease. In some cases, treatment may be advised prior to demonstration of extraocular disease. (The authors are grateful for the contributions to this legend by Drs. Vikas Khetan and Zhao Jun Yang.)


Figure 8.53 Retinoblastoma Following External Beam Radiation

Facial deformity is the result of bilateral external beam radiotherapy administered in infancy for bilateral retinoblastoma. The right eye was later enucleated. The left eye has radiation cataract. Whenever possible, it is desirable to avoid external beam radiation of treating retinoblastoma.




Figure 8.54 Trilateral Retinoblastoma

Primitive neuroectodermal tumor (PNET) in association with bilateral retinoblastoma presented in this child first as a brain tumor. Usually the intracranial tumor originates in the pineal gland. Since external beam radiation of infants is now rarely used as primary treatment for retinoblastoma, replaced by chemotherapy, the frequency of trilateral retinoblastoma has decreased markedly. Treatment of trilateral retinoblastoma includes extensive therapy including systemic chemotherapy, intrathecal chemotherapy, and high-dose chemotherapy with stem cell transplant rescue, as well as local therapy to the eye tumors. (The authors are grateful for the contributions to this legend by Drs. Vikas Khetan and Zhao Jun Yang.)


Figure 8.55 Retinoblastoma Secondary Tumor

This computed tomography scan shows glioblastoma multiforme (2nd tumor) in a patient with bilateral retinoblastoma after radiation therapy. Radiation can induce second nonocular malignancies in the radiated field. Second tumors outside the field may also develop in patients with retinoblastoma later in life. (The authors are grateful for the contributions to this legend by Drs. Vikas Khetan and Zhao Jun Yang.)