Case of the Month

Edited by Robert N. Johnson, MD

Case History

An 11-year-old boy presents with a 1-month history of decreased vision in his left eye.¹ His parents also report that he has had increasing difficulty with night vision.  His past ocular history was negative and his past medical history was significant only for asthma. Family history and review of systems was noncontributory.

On examination, the best-corrected visual acuity was 20/25 in the right eye and count fingers in the left eye. Ocular motility, pupillary examination, intraocular pressure, and anterior segment examinations were normal in both eyes. The posterior segment examination of the right eye revealed a normal optic nerve , with light grayish mottling of the retinal pigment epithelium in the macula extending peripherally (Figure 1A, 1C). In the mid to far peripheral retinal, retinal pigment epithelial mottling with pigmented bone-spicule changes was noted. There were also telangiectatic vessels with perivascular exudates in the inferior midperiphery (Figure 1C). Dilated fundus examination of the left eye showed prominent exudation in the peripapillary area and the macula (Figure 1B, D). Peripherally, massive exudation with serous retinal detachment inferiorly was present (Figure 1D), as well as a similar pattern of retinal epithelial mottling and bone-spicule pigmentation.

Fluorescein angiography demonstrated significant disk leakage in both eyes, macular hyperfluorescence and marked diffuse leakage in the left eye (Figure 2A and B).

A 24-2 Humphrey visual field detected severely constricted visual fields most prominently in the left eye. The electrooculogram (EOG) was abnormal and the electroretinography (ERG) showed subnormal photopic and scotopic responses in both eyes.

Figures 2A and B: Fluorescein angiogram montages of the right and left eye. Note the disc leakage in both eyes as well as macular hyperfluorescence. The background fluorescence is increased in both eyes due to retinal pigment epithelial attenuation.

Differential Diagnosis

Retinitis pigmentosa, Coats disease, retinal capillary hemangioma, retinoblastoma, familial exudative vitreoretinopathy, chronic retinal detachment, Vogt-Koyanagi-Harada syndrome, acute retinal necrosis, and toxoplasmosis.

Additional Case History

Multiple treatment options were considered for the patient, including laser photocoagulation, cryotherapy, and anti-VEGF injections.  Due to the underlying condition of retinitis pigmentosa and the peripapillary location of leakage, destructive procedures were deferred in favor of anti-VEGF injections.  The patient received seven consecutive intravitreal bevacizumab injections on a monthly basis.  After four injections, significant improvement in subfoveal exudates and serous retinal detachment were appreciable (Figure 3A and 3B).  After the seventh injection, all subfoveal exudates and detachment had resolved, with visual improvement to 20/80 in the left eye.  At the patient’s 10-year follow-up visit, his vision was 20/25 in both eyes and he has had no recurrence of exudation or detachment.  Bone spicule changes are visible in the periphery of both eyes, with subretinal fibrosis and scarring present inferiorly (Figure 4A and 4B).  Ocular coherence tomography (OCT) of both eyes revealed global loss of the nerve fiber layer, except in the peripapillary area, as well as severe outer retinal thinning with relative sparing of the fovea (Figure 5A and 5B).  A mild epiretinal membrane is also present in both eyes.

Figures 4A and B: Fundus color photograph montage of the right and left eyes, 10 years later. Note the peripheral bone-spicule changes in both eyes with areas of subretinal fibrosis inferiorly. The massive exudation noted on presentation in the left eye remains resolved.

Figures 5A and B: Ocular coherence tomography scan of the right eye (A) shows severe outer retinal thinning with sparing of the fovea, mild inner retinal degeneration except in the peripapillary area and a mild epiretinal membrane.  Enhanced definition 12mm optical coherence scan of the left eye (B) shows similar findings with severe outer retinal thinning (sparing the fovea), mild inner retinal degeneration and a mild epiretinal membrane.

Discussion

Retinitis pigmentosa (RP) refers to a group of inherited disorders that are characterized by a progression from dysfunction to cell loss and eventually atrophy of retinal tissue.²  While the disorder is predominantly due to rod photoreceptor dysfunction, it leads to subsequent degeneration of cones and the retinal pigment epithelium.  RP may present in isolation, known as typical RP, or in association with systemic disease, referred to as syndromic RP.  The overall prevalence is 1:3000 to 1:5000.²  It may occur as a sporadic disease, or be inherited in an autosomal dominant, autosomal recessive, or X-linked fashion.

Retinitis pigmentosa with Coats’-like exudative vasculopathy (Coats’-like RP) is a well-documented, rare condition, with its estimated incidence ranging from 1.2% to 3.5% of patients with RP.³ Similar to Coats’ disease, it is characterized by the striking appearance of yellow retinal or subretinal lipid deposits associated with overlying dilated, tortuous telangiectatic vessels.  It can also be often associated with serous retinal detachments, most commonly located in the dependent inferior retina.  However, unlike Coats’ disease, it is commonly bilateral, equally prevalent in both genders, and affects older patients.

The two hallmark features of retinitis pigmentosa are nyctalopia and visual field loss.² The nyctalopia of retinitis pigmentosa is accompanied by narrowing of the visual field, causing disorientation and a propensity for accidents in dim light. Visual field loss of RP is usually most severe superiorly, due to early involvement of the inferior retina.  Patients with Coats’-like RP may also have a sudden, fairly rapid decline in vision, particularly with daytime or reading vision.³

 The classic fundus appearance of RP demonstrates severely attenuated retinal vasculature, bone spicule pigmentary deposits, and waxy pallor of the optic nerve.  In patients with the Coats’-type, dilated, aneurysmal, or telangiectatic retinal veins are often found overlying areas of lipid and exudative detachment.  The deposition of lipid is usually multifocal, subretinal, equatorial, at the posterior edge of an exudative detachment, and involving the inferior and/or temporal quadrants.³  In addition to the classic angiographic findings of RP, such as cystoid macular edema, transmission defects caused by loss of retinal pigment epithelium, and blockage of the choroidal fluorescence in areas of pigment clumping, those with Coats’-like RP will demonstrate leakage in the areas of the telangiectatic vessels.  The visual field is often less than 10 degrees and the electroretinogram is usually extinguished or nearly extinguished at presentation.

Although a wide variety of genes have been associated with retinitis pigmentosa, it is hypothesized that mutations in the human homologue of Drosophila crumbs gene (CRB1) may put patients at risk for developing the Coats’-like form of RP.⁴  However, this is an imperfect association as there have been reports of CRB1-negative Coats’-like RP,⁵ and even the original study reported affected siblings of patients with Coats’-like RP who did not develop the Coats’-like complication.⁴  Therefore, while a CRB1 mutation may be helpful in diagnosis, other environmental and genetic factors are also playing a significant role in pathogenesis.

Treatment options for Coats’-like RP include: laser photocoagulation of telangiectatic and neovascular vessels, cryotherapy, anti-VEGF injections, intravitreal steroid, and surgery, including scleral buckling with subretinal fluid drainage and pars plana vitrectomy with or without perfluorocarbon.  Laser photocoagulation is the most widely accepted initial treatment modality, but the presence of an exuberant serous retinal detachment may preclude its use.  Intravitreal bevacizumab has been used with success in case reports of Coats’ disease, both in isolation and as an adjunctive to laser therapy.⁶  Our case is the only example in the literature of the successful use of Avastin monotherapy in Coats-like RP.¹  Overall, due to the variable natural history of this disease, no particular intervention has been shown to be uniformly beneficial in all patients.

We would like to acknowledge Drs. Yang, Borirakchanyavat, Chan-Kai, Stout and Fu who originally presented this case in Retina, Diagnostics and Therapeutics Challenge.¹

References

1. Yang S, Borirakchanyavat S, Chan-Kai BT, Stout JT, Fu AD. Diagnostic and therapeutic challenges. Retina. 2009;29(5):708-14.
2. Weleber RG, Gregory-Evans K. Retinitis pigmentosa and allied disorders. In: Ryan SJ, ed. Retina, 4th edn. Philadelphia, PA: Elsevier; 2006:394-485.
3. Khan JA, Ide CH, Strickland MP. Coats’-type retinitis pigmentosa. Surv Ophthalmol 1988;32:317-332.
4. Den Hollander AI, Heckenlively JR, van den Born LI, de Kok YJ, van der Velde-Visser SD, Kellner U, Jurklies B, van Schooneveld MJ, Blankenagel A, Rohrschneider K, Wissinger B, Cruysberg JR, Deutman AF, Brunner HG, Apfelstedt-Sylla E, Hoyng CB, Cremers FP. Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the crumbs homologue 1 (CRB1) gene. Am J Hum genet 2001;69(1):198-203.
5. Sarao V, Veritti D, Prosperi R, Pignatto S, Lanzetta P. A Case of CRB-1 negative Coats-like retinitis pigmentosa. J AAPOS 2013;17(4):414-6.
6. Villegas VM, Gold AS, Berrocal AM, Murray TG. Advanced Coats’ disease treated with intravitreal bevacizumab combined with laser vascular ablation. Clin Ophthal 2014;8:973-976.