2020–2021 BCSC Basic and Clinical Science Course™
6 Pediatric Ophthalmology and Strabismus
Part II: Pediatric Ophthalmology
Chapter 25: Disorders of the Retina and Vitreous
Congenital and Developmental Abnormalities
Hereditary vitreoretinopathies include a broad range of disease entities. The ones discussed here characteristically present in childhood.
Juvenile retinoschisis (splitting of the retina) is an X-linked disease caused by mutations in the RS1 gene, which encodes for the retinal protein retinoschisin, an adhesion protein that is believed to be essential to the health of Müller cells. Affected males usually present in early childhood with decreased vision. Visual acuity varies but usually deteriorates to roughly 20/200.
Figure 25-17 Best disease. A, Left eye with vitelliform lesion and central dome-shaped choroidal neovascular membrane (CNVM). B, Right eye with central macular hyperautofluorescence due to vitelliform material, as seen on FAF imaging. C, Fluorescein angiography image (right eye) reveals central macular hyperfluorescence due to staining of vitelliform material. D, Fluorescein angiography image (left eye) shows late central hyperfluorescence from leakage of CNVM. E, Spectral-domain OCT (SD-OCT) image (right eye) reveals subretinal hyperreflective material with a hyporeflective cleft corresponding to the vitelliform lesion. F, SD-OCT image (left eye) reveals a large subfoveal pigment epithelial detachment with subretinal hyperreflective material and subretinal fluid.
(Courtesy of Marc T. Mathias, MD.)
Foveal retinoschisis is present in almost all cases; peripheral retinoschisis, in approximately 50% of patients. The fovea has a stellate or spokelike configuration that may resemble cystoid macular edema; it becomes less distinct over time. SD-OCT shows schisis spaces in the middle layers of the macula (Fig 25-18A). Vitreous veils or strands are common, and vitreal syneresis, or liquefaction, is prominent. Complications include vitreous hemorrhage and various types of retinal detachment (Figs 25-18B, 25-19). The ERG shows a reduction of the scotopic b-wave with preservation of the a-wave.
Contact sports should be avoided because the retina in affected eyes is more susceptible to trauma. Gene replacement has shown some success in mouse models. Use of carbonic anhydrase inhibitors to treat cystic macular lesions is under investigation.
Verbakel SK, van de Ven JP, Le Blanc LM, et al. Carbonic anhydrase inhibitors for the treatment of cystic macular lesions in children with X-linked juvenile retinoschisis. Invest Ophthalmol Vis Sci. 2016;57(13):5143–5147.
Figure 25-18 Juvenile retinoschisis. A, SD-OCT image shows schisis of retina. B, Combined tractional and rhegmatogenous retinal detachment.
(Courtesy of Scott C. Oliver, MD.)
Figure 25-19 Three-year-old with juvenile retinoschisis. A, Central and extensive peripheral retinoschisis with mild vitreous and preretinal hemorrhage. There is a large circumferential tractional retinal detachment around the arcades, encroaching on the central macula. A retinal hole is also present. B, Fluorescein angiography reveals an extensive tractional detachment. C, Macular OCT image demonstrates retinoschisis with a tractional detachment and subretinal fluid encroaching on the fovea.
(Courtesy of Marc T. Mathias, MD.)
Stickler syndrome is a group of connective tissue disorders with variable phenotypic expression. The most common type of Stickler syndrome is autosomal dominant, has ocular and systemic findings, and is caused by a mutation in COL2A1, the gene that encodes for type II procollagen. Some mutations in the gene cause an ocular-only phenotype.
The diagnosis is made based on the clinical features as well as the results of genetic testing. Common ocular abnormalities include an optically empty vitreous due to vitreous liquefaction, high myopia, lattice degeneration, and proliferative vitreoretinopathy. In addition, there is a high incidence of retinal detachment secondary to retinal breaks. Anterior chamber angle anomalies, ectopia lentis, cataracts, ptosis, and strabismus are less common.
Characteristic systemic abnormalities are a flat midface, progressive hearing loss, cleft palate, Pierre Robin sequence, mitral valve prolapse, and progressive arthropathy with spondyloepiphyseal dysplasia. Although the arthropathy may not be symptomatic initially, children with Stickler syndrome often show radiographic abnormalities of the long bones and joints, and associated symptoms develop.
The retinal detachments are often difficult to repair because these patients may have large retinal breaks posteriorly and the incidence of proliferative vitreoretinopathy is high. The incidence of vitreous loss during cataract surgery is high, as is the rate of subsequent retinal detachment. Retinal folds and breaks should be treated before cataract extraction. Prophylactic retinopexy may be appropriate in certain patients.
Fincham GS, Pasea L, Carroll C, et al. Prevention of retinal detachment in Stickler syndrome: the Cambridge prophylactic cryotherapy protocol. Ophthalmology. 2014;121(8):1588–1597.
Knobloch syndrome is a vitreoretinopathy caused by biallelic mutations in COL18A1. It is classically defined by the triad of occipital encephalocele, high myopia, and predisposition to retinal detachment.
The ocular phenotype is characterized by a distinct vitreoretinal degeneration—very severe RPE atrophic changes with prominent choroidal vessels (Fig 25-20A) out of proportion to the degree of myopia, macular atrophic lesions with or without a “punched-out” appearance, and white fibrillar vitreous condensations. These eyes have a strong predisposition to spontaneous retinal detachment. Smooth (cryptless) irides are universal in affected eyes (Fig 25-20B); ectopia lentis is an occasional finding. Taken together, these ocular findings are pathognomonic for biallelic COL18A1 mutations.
Figure 25-20 Knobloch syndrome. A, With severe chorioretinal atrophy. B, With cryptless iris. C, With scalp abnormality.
(Courtesy of Arif O. Khan, MD.)
ERG shows cone–rod dysfunction. Pigment dispersion glaucoma has been reported in 2 patients.
Systemic manifestations are variable and not always present; they include occipital abnormalities (Fig 25-20C) (ranging from scalp abnormalities to encephalocele), congenital renal malformations, developmental delay, seizures, and heterotopic gray matter.
Therapy is based on disease manifestations.
Khan AO, Aldahmesh MA, Mohamed JY, Al-Mesfer S, Alkuraya FS. The distinct ophthalmic phenotype of Knobloch syndrome in children. Br J Ophthalmol. 2012;96(6):890–895.
Norrie disease is an X-linked recessive disorder of retinal dysplasia caused by a mutation in the NDP gene, which encodes for the protein norrin. Affected boys are typically born blind and have varying degrees of hearing impairment and intellectual disability.
The condition is characterized by a distinctive retinal appearance: a globular, severely dystrophic retina with pigmentary changes in the avascular periphery. During the first few days or weeks of life, a bilateral, yellowish retinal detachment appears, followed by a whiter mass behind the clear lens. Over time, the lenses, and later the cornea, opacify; phthisis bulbi may ensue by age 10 years or earlier. Female carriers show peripheral retinal abnormalities.
No treatment exists.
Familial exudative vitreoretinopathy
Familial exudative vitreoretinopathy (FEVR) is a disease of abnormal retinal vascularization similar to that seen in ROP (discussed earlier in the chapter). There is failure of the peripheral retina to vascularize. FEVR is typically autosomal dominant, but autosomal recessive and X-linked forms exist as well, the latter resulting from mutations in the same gene involved in Norrie disease (NDP).
Posterior pole findings in FEVR include retinal traction, folds, breaks, and detachment secondary to vitreous traction (Fig 25-21A). Posterior vitreous detachment and thick peripheral intraretinal and subretinal exudates may develop (Fig 25-21B). The disease is bilateral and can mimic ROP but affects infants born at full term. Fluorescein angiography shows areas of retinal nonperfusion and neovascularization (Fig 25-21C). Examination of family members is important in the diagnosis of FEVR. Affected family members can show marked variation in severity, from minimal straightening of retinal vessels and peripheral nonperfusion to total retinal detachment.
Figure 25-21 Familial exudative vitreoretinopathy. A, Tractional retinal detachment with a knot of anterior fibrotic tissue. B, Tractional detachment treated with a radially oriented sponge. Note the subretinal exudates. C, Fluorescein angiography image shows peripheral avascular retina and hyperfluorescence from leakage of peripheral vessels.
(Courtesy of Scott C. Oliver, MD.)
Cryopexy, photocoagulation, vitrectomy, and cataract surgery have been used to manage patients with this disorder.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.