A 24-year-old female patient presented to our clinic with complaints of decreased vision and nyctalopia. Her symptoms had been progressively worsening over time. Her personal medical history was unremarkable. There was consanguinity between her parents, although no similar ocular complaints were reported among other family members.
On ophthalmologic examination, the best corrected visual acuity (BCVA) was approximately 0.6 in the right eye and 0.7 in the left eye. Anterior segment evaluation revealed bilateral posterior subcapsular cataracts. Intraocular pressure was measured at 16 mmHg in the right eye and 19 mmHg in the left eye. Fundus examination showed peripheral pigmentary changes with a yellowish foveal reflex, consistent with findings of Goldmann-Favre syndrome. Following the clinical diagnosis, genetic testing was performed, which confirmed the diagnosis by identifying a pathogenic mutation in NR2E3 gene consistent with Goldmann-Favre syndrome.
In color fundus photograph of the right/left eye, the macula displays a yellowish reflex, suggestive of underlying foveoschisis or retinal disorganization. The peripheral retina shows scattered pigmentary alterations resembling bone-spicule–like deposits. But note that they are oval in shape, unlike the bone spicules in retinitis pigmentosa. Retinal vessels are slightly attenuated, and the optic disc appears mildly pale, features that may emerge in the chronic phase of the disease. Notably, the peripheral involvement is limited compared to what is typically seen in retinitis pigmentosa. As seen in the figure, hyperpigmented areas extend up to the points indicated by the arrows; However, beyond the arrows, no hyperpigmented areas are observed in far peripheral retina. further supporting the diagnosis of Goldmann-Favre syndrome.
Fundus autofluorescence (FAF) imaging reveals a speckled pattern of hyperautofluorescence throughout the central macula, consistent with areas of retinal schisis and photoreceptor layer disruption. There is an absence of the typical hyperautofluorescent ring commonly observed in retinitis pigmentosa, supporting the diagnosis of Goldmann-Favre syndrome. Patchy hypoautofluorescent zones are seen throughout vascular arcades and mid-periphery, corresponding to pigment clumping and RPE degeneration. In the area indicated by the arrows, hypoautoflurescent regions suggestive of RPE hyperplasia are observed; however, beyond the arrows, no such areas are present. The macular region appears relatively preserved, although subtle changes in autofluorescence may reflect early foveal involvement.
Spectral-domain optical coherence tomography (SD-OCT) of the macula demonstrates pronounced intraretinal schisis cavities, particularly involving the inner nuclear and outer plexiform layers, consistent with foveoschisis. The retinal layers appear disorganized, with splitting of both inner and outer retinal structures. The external limiting membrane (ELM) remains partially intact, while the ellipsoid zone is poorly delineated, reflecting photoreceptor disruption. There is no evidence of subretinal fluid or typical cystoid macular edema. These findings are characteristic of Goldmann-Favre syndrome and differentiate it from retinitis pigmentosa, in which schitic changes are not typically observed.
Goldmann-Favre syndrome is a rare inherited vitreoretinal dystrophy characterized by a combination of retinal degeneration and structural disorganization. It typically presents with progressive night blindness, decreased visual acuity, and visual field constriction, often beginning in early adulthood. Distinctive clinical findings include foveoschisis, peripheral retinoschisis, vitreous veils or opacities, and punctate pigmentary changes, especially in the mid-peripheral retina. Unlike retinitis pigmentosa, Goldmann-Favre syndrome does not usually exhibit widespread peripheral photoreceptor loss or a classic hyperautofluorescent ring on FAF imaging. OCT imaging frequently reveals multilayer schisis at the macula, particularly involving the inner nuclear and outer plexiform layers. The condition follows an autosomal recessive inheritance pattern and is associated with mutations in the NR2E3 gene, which plays a role in retinal development and photoreceptor differentiation. Accurate diagnosis relies on a combination of multimodal imaging and genetic testing.
The fundus typically shows mid-peripheral pigmentary changes resembling bone spicules, a slightly waxy disc, and a yellowish foveal reflex. In contrast to RP, where there is prominent peripheral pigment clumping and widespread atrophy, Goldmann-Favre syndrome exhibits more central and mid-peripheral involvement without extensive peripheral photoreceptor loss. Additionally, vitreous veils and membranous changes may be noted, which are uncommon in RP. FAF often reveals a mottled pattern of hyper- and hypoautofluorescence in the posterior pole. A key distinguishing feature is the absence of the typical hyperautofluorescent ring seen in RP, which represents the border between functional and degenerating photoreceptors. In Goldmann-Favre syndrome, this ring is usually lacking, reflecting the disease’s more structural than purely photoreceptor-driven pathology. OCT is a critical modality for distinguishing Goldmann-Favre from RP. In GF, foveoschisis—splitting of the inner and outer retinal layers—is a hallmark finding. Intraretinal cystic spaces are common, especially within the inner nuclear and outer plexiform layers. RP, on the other hand, typically shows progressive thinning of the outer retinal layers, ellipsoid zone disruption, and photoreceptor loss without schisis formation.
There is currently no definitive cure for Goldmann-Favre syndrome, and treatment remains largely supportive and symptomatic. Management strategies may include the use of carbonic anhydrase inhibitors (e.g., topical or oral acetazolamide) to reduce macular schisis and improve visual acuity. Cataract surgery may be considered in cases of visually significant posterior subcapsular cataract, which is commonly associated with the disease. Regular monitoring with OCT is essential to assess the stability or progression of schitic changes. Genetic counseling is also recommended, given the autosomal recessive inheritance pattern. Emerging gene-based therapies remain under investigation but are not yet clinically available.
Credit: M. Giray Ersoz, MD, FEBO
Biruni University School of Medicine, Department of Ophthalmology, Istanbul, Turkey
Instagram accounts: @retina.review and @retina.dr.girayersoz
and Sepideh Lotfi, MD
Biruni University School of Medicine, Department of Ophthalmology, Istanbul, Turkey
Instagram accounts: @sepidls