Posterior polymorphous corneal dystrophy type 3 (PPCD3) is an autosomal dominant endothelial dystrophy caused by variations in the ZEB1 gene. We report a pediatric case presenting with progressive visual impairment associated with simultaneous features of corneal ectasia and endothelial dystrophy. A 9-year-old boy presented with progressive diminution of vision and high myopia. Slit-lamp examination revealed prominent corneal nerves, and central corneal steepening, along with diffuse endothelial guttae and a beaten-metal appearance of the endothelium. Multimodal imaging including Scheimpflug tomography that demonstrated marked bilateral corneal steepening with tomographic features suggestive of corneal ectasia (Kmax 59.0 D in the right eye and 61.6 D in the left eye). Interestingly, central corneal thickness was increased (636 µm in the right eye and 659 µm in the left eye), feature atypical of keratoconus. Specular microscopy demonstrated reduced endothelial cell density. Whole-exome sequencing of the proband identified a novel heterozygous splice-site variant in ZEB1 (chr10:g.31510671A > T; c.485-2A > T), affecting the canonical 3' splice acceptor site. Targeted next-generation sequencing of parental blood samples confirmed the variant in the father (heterozygous) and its absence in mother, consistent with paternal inheritance. This case provides additional evidence supporting the recognized association between ZEB1-related PPCD3 and suspected corneal ectasia, while describing a novel splice-site ZEB1 variant.
INTRODUCTION:PCARE-associated inherited retinal diseases are rare disorders characterized by progressive vision loss due to photoreceptor degeneration. Although several variants have been identified in diverse populations, limited data are available from the Iberian Peninsula. METHODS:We conducted a retrospective case series of eight Portuguese patients from six unrelated families with confirmed PCARE mutations. Clinical data, multimodal imaging, and genetic analyses were reviewed. RESULTS:The most common variant identified was c.3099delinsCCAGG p.(Val1034Glnfs *74), present in homozygosity in five patients from 4 families and in heterozygosity with a variant of uncertain significance in one patient, suggesting a potential regional founder effect. All patients exhibited symptoms beginning in the third to fifth decades, primarily decreased visual acuity, visual field constriction, photophobia, and nyctalopia. Fundoscopy findings included bone spicule, perifoveal retinal atrophy with foveal sparing, and arteriolar narrowing. Optical coherence tomography showed thinning of the outer retinal layers. Two patients also showed foveal involvement and severe visual loss. The clinical phenotype was consistent with both rod-cone and cone-rod dystrophy. CONCLUSION:Our findings suggest that this variant may be enriched in the Portuguese population. Further studies are needed to confirm the founder effect hypothesis and to guide future therapeutic strategies targeting PCARE-associated retinal degeneration.
PURPOSE:We report the detailed ophthalmological evaluation of two affected members of the same family (mother and son) carrying the heterozygous pathogenic CRX frameshift variant (NM_000554.6:c.661del; p. Tyr221Thrfs *9), both presenting with photophobia and photopsia but exhibiting markedly different clinical manifestations. METHODS:Both individuals underwent comprehensive ophthalmological assessment, including best-corrected visual acuity, multimodal retinal imaging (ultra-widefield fundus autofluorescence, ultra-widefield pseudocolor imaging, and spectral-domain optical coherence tomography, full-field electroretinography, kinetic perimetry, full-field stimulus threshold testing (FST), and chromatic pupillometry. The CRX variant was identified by next-generation sequencing and confirmed by Sanger sequencing in the mother. RESULTS:The 45-year-old son was diagnosed with cone dystrophy (COD), characterized by progressive central visual loss, cone dysfunction on electroretinography, and a distinctive bifocal retinal degeneration involving both the macula and nasal retina. In contrast, his 71-year-old mother exhibited a milder macular-confined phenotype consistent with macular dystrophy (MD), with normal full-field electroretinography and structural abnormalities limited to the macula on optical coherence tomography. CONCLUSIONS:The marked differences in functional and structural findings support variable intrafamilial expressivity. To our knowledge, this is the first report associating the c.661del (p. Tyr221Thrfs *9) variant with cone dystrophy presenting as bifocal retinal degeneration, thereby expanding both the phenotypic spectrum associated with this variant and the mutational spectrum of CRX-associated bifocal retinal degeneration.
INTRODUCTION:Hypotrichosis with juvenile macular dystrophy (HJMD) is a rare autosomal recessive disorder caused by pathogenic variants in the CDH3 gene. Most reported cases have occurred in Middle Eastern and Asian populations, and individuals of African ancestry remain markedly underrepresented in inherited retinal disease cohorts and genomic reference databases. Here, we report the first published case of suspected CDH3-related HJMD in a Black patient. METHODS:Clinical evaluation included visual acuity, fundus examination, and SD-OCT. Genome sequencing was performed with copy number variant analysis and in silico tools were used to predict pathogenicity. Maternal segregation analysis was also performed. RESULTS:The patient presented in childhood with progressive central macular atrophy and longstanding scalp hypotrichosis, but early genetic testing suggested an alternative diagnosis. Subsequent whole-exome sequencing identified two heterozygous variants in CDH3: an unreported exon 2 deletion (chr16:68679423_68691379) predicted to cause loss of P-cadherin protein function and classified as likely pathogenic under ACMG criteria, and an extremely rare missense variant (c.1658T > A; p.(Ile553Asn)) classified as a variant of uncertain significance but predicted by in silico modeling to destabilize P-cadherin. DISCUSSION:With the patient's characteristic syndromic presentation, these findings supported a clinical diagnosis of HJMD. This case underscores the importance of careful phenotyping and reevaluation with updated comprehensive genomic testing when initial results are nondiagnostic or inconsistent with presentation. Documenting rare CDH3 variants in an underrepresented population contributes to the expanding mutation spectrum of CDH3 and may improve future genotype-phenotype interpretation.
Introduction: lthough Leber hereditary optic neuropathy (LHON) is primarily an optic neuropathy, systemic comorbidities across the disease timeline have not been systematically described. We aimed to describe systemic comorbidities documented before and after LHON onset.Methods: We retrospectively reviewed medical records of 187 genetically confirmed patients with LHON (m.11778G>A, m.14484T>C, or m.3460G>A) seen at a single center between January 1990 and March 2025. Systemic comorbidities were extracted, standardized, coded into prespecified categories, and classified as present before onset or newly documented after onset. Findings were summarized as cumulative event counts and percentages; multiple events per patient were allowed.Results: The cohort comprised 156 males (83.4%) and had a median age at onset of 32.0 years. Before onset, 68 comorbidity events were recorded; alcohol-related, lifestyle-related, and gastrointestinal conditions were most frequent (12 events each). After onset, 27 newly documented events were recorded; mental health disorders were most frequent (nine events), followed by lifestyle-related conditions (five events).Discussion: Alcohol-related conditions were more commonly documented before onset, whereas mental health disorders were more commonly documented after onset. Early assessment of health behaviors and nutrition, and systematic attention to mental health after onset, may support comprehensive LHON care. These findings do not establish increased prevalence or causality.
PURPOSE:Van den Ende-Gupta syndrome (VDEGS) is a rare autosomal recessive disorder caused by biallelic variants and characterized by blepharophimosis, arachnodactyly, congenital joint contractures, and a recognizable craniofacial phenotype, with normal growth and intelligence. The ophthalmic phenotype beyond blepharophimosis is sparsely described, and sclerocornea has been reported in only two molecularly confirmed patients to date. We describe the ocular phenotype of a 7-month-old male infant with molecularly confirmed VDEGS due to a recurrent Saudi founder variant. METHODS:A single case report of a 7-month-old male of consanguineous Saudi parents referred for photophobia and small-appearing eyes, coupled with a focused review of the published ophthalmic phenotype of VDEGS. RESULTS:Examination revealed bilateral blepharophimosis with epicanthus inversus and bilateral, asymmetric peripheral sclerocornea with loss of limbal demarcation and no vascularization, with a symmetric and good red reflex bilaterally. Cycloplegic refraction demonstrated clinically significant spherical hyperopic anisometropia (+6.00 OD versus +3.00 OS) placing the patient at substantial risk for anisometropic amblyopia, a refractive finding not previously documented in VDEGS. The visual axis was not entirely obscured, and the patient maintained good following and fixation in both eyes. Whole-exome sequencing identified a homozygous pathogenic variant (NM_153334.7: c.190T>C, p.(Cys64Arg)), a recurrent Saudi founder allele, confirming the diagnosis of VDEGS. CONCLUSION:This report expands the ocular phenotype associated with the recurrent c.190T>C founder variant to include bilateral peripheral sclerocornea and clinically significant hyperopic anisometropia, further supporting biallelic dysfunction as sufficient to disrupt anterior segment development.
Diabetic retinopathy (DR) requires robust biomarkers. To overcome the limitations of bulk sequencing, we integrated single-cell eQTL mapping with Mendelian randomization to identify causal cell populations and genes. CD8 Teff cells were expanded in peripheral blood, showing elevation in non-DR diabetes and reaching maximal levels in DR. Mendelian randomization analysis implicated IL2RB as a putative causal marker, with the lead eQTL SNP rs3184504 demonstrating strong association (p = 8.5467 × 10-18). Colocalization analysis with DR GWAS and validation in bulk data reinforced this signal. In tissues, CellChat predicted more interactions for IL2RB+ compared to IL2RB- CD8 Teff cells, including IL16-CD4 with macrophages and NAMPT interactions with both ITGA5+ITGB1 and INSR on endothelial cells, implicating immune-vascular regulation. Together, these findings nominate IL2RB as a biomarker and therapeutic target while clarifying mechanisms underlying DR.
INTRODUCTION:BAP1 tumor predisposition syndrome (BAP1-TPDS) is an autosomal dominant syndrome associated with uveal melanoma and multiple systemic malignancies, which is believed to be underreported. Recently, the presence of polydactylous onychopapillomas were deemed an associated phenotype of BAP1-TPDS. Here we describe a case of choroidal melanoma in a patient with polydactylous onychopapilloma, as well as extensive family history of both BAP1-TPDS and relevant nail findings. METHODS:A retrospective chart review was conducted. RESULTS:A 62-year-old man presented with choroidal melanoma of the left eye. Tumor genetic expression profiling demonstrated Class 2, PRAME-negative status, and next-generation sequencing identified variants in GNAQ and BAP1 (c.123-12_127delTACTTCCCCCAGCCCTG), with the BAP1 splice-site variant present at a high variant allele frequency (91.3%). Physical examination revealed onychopapillomas affecting multiple digits and a family history of malignancy among first-degree relatives. Germline multi-cancer panel testing confirmed a hereditary BAP1 variant, establishing the diagnosis of BAP1-TPDS. The patient underwent plaque brachytherapy with continued tumor regression and is enrolled in multidisciplinary surveillance for BAP1-associated malignancies; genetic testing was recommended for close relatives. DISCUSSION:This case underscores the importance of combining tumor sequencing with careful phenotypic assessment and family history review. Recognition of polydactylous onychopapillomas may serve as a valuable clinical clue prompting germline testing for BAP1-TPDS in uveal melanoma patients.
BACKGROUND:Gene variants in the unfolded protein response regulator activating transcription factor 6 (ATF6) are linked to achromatopsia (ACHM), an autosomal recessive cone dystrophy that impairs color vision and visual acuity. While most known variants appear in the transcriptional activator cytosolic region, the function and clinical impact of stress-sensing luminal domain variants remain poorly understood. METHODS:A patient with ACHM from a family carrying a new luminal domain ATF6 variant was clinically evaluated. Genetic testing was performed and compared to reference ATF6 sequence NM_007348.4. Deleterious ATF6 variants were analyzed using gnomAD allele frequencies, Combined Annotation Dependent Depletion (CADD) scores, multispecies sequence alignment, and spliceAI delta scores. RESULTS:An 18-year-old male from Taiwan presented with a homozygous missense exonic splice-region variant (c.1604G>A, p.Ser535Asn), bilateral foveal hypoplasia, disrupted inner outer photoreceptor segment layers, impaired color vision, and absent photopic but preserved scotopic responses. All known deleterious ATF6 variants had gnomAD frequencies below 0.0000627, and most were predicted to be deleterious by CADD. CONCLUSIONS:Clinical and genetic characterization of this new luminal ATF6 variant in an affected individual highlights the critical importance of the ATF6 stress-sensing luminal domain for normal visual function.
CEP290-associated retinal diseases span a broad phenotypic spectrum, from Leber congenital amaurosis to milder retinal dystrophies to syndromic ciliopathies. Herein, we describe a non-syndromic 18-year-old woman with compound heterozygous pathogenic variants in CEP290 whose ophthalmic features are infantile-onset nystagmus, benign and stable fundus appearance, and lack of cone-mediated visual and retinal function. Serial examinations from infancy onward document stable achromatopsia-like ophthalmic features. No cone-mediated vision or retinal function was demonstrated. By optical coherence tomography, foveal architecture was preserved and central retinal thickness was stable for more than a decade (median 246 µm, range 232-257 µm). Testing for common CNGA3 and CNGB3 variants in early childhood was negative, as was further testing via an eight-gene achromatopsia panel. Trio exome sequencing identified compound heterozygous pathogenic CEP290 variants in trans: c.4723A>T (p.Lys1575Ter) and c.6277del (p.Val2093SerfsTer4). Notably, c.4723A>T is a nonsense variant previously shown to undergo nonsense-associated exon skipping, consistent with a hypomorphic effect that has been associated with milder CEP290-related retinal disease. These findings suggest a selective impairment of cone-mediated function with relative preservation of rod function.
PURPOSE:This study aimed to report the longitudinal Ora Visual Navigation Course (Ora VNC™) mobility test results in two individuals, with CEP290 LCA following intravitreal injections of an antisense oligonucleotide, sepofarsen. METHODS:Two individuals were enrolled in the Illuminate Phase 3 trial and subsequently in the Post-Trial Access (PTA) program, undergoing Ora VNC™ across 12 visits. RESULTS:Subject 1 was initially randomized to the control (sham) group and switched to treatment from control group from the month 12 visit onwards. This individual passed only a few courses but demonstrated signs of enhanced spatial perception (defined by, among others, the ability to perceive objects' shapes and sizes). FST (full-field stimulus threshold) supported the light sensitivity gain in this subject. In contrast, subject 2, who received treatment since baseline visit, successfully completed mobility tests in all visits with progressive improvement, reaching lower luminance and more challenging contrast settings over time. According to the technicians' report, both subjects demonstrated an increase in perceived obstacle recognition during iterations, which may reflect improvement of mobility-based visual function outcomes. CONCLUSION:The Ora VNC™ mobility test captured mobility-based visual function gains, including subtle spatial improvements, but may lack sensitivity in individuals with extremely low vision, potentially overlooking small but patient-relevant changes.
INTRODUCTION:Gene therapy with voretigene neparvovec-rzyl was approved primarily based on improvements observed in the Multi-Luminance Mobility Test (MLMT), while the full-field stimulus threshold (FST) test, a secondary endpoint, also demonstrated efficacy. However, the MLMT is difficult to apply in routine practice, and the FST does not provide spatial information regarding retinal function, which limits direct structural-function correlation. PURPOSE:Therefore, this study investigated whether microperimetry could serve as a simpler, more practical alternative by evaluating its changes after this gene therapy. METHODS:Mean sensitivity and fixation parameters were evaluated in a cohort of 5 patients (10 eyes) who underwent microperi-metry following gene therapy in São Paulo, Brazil. RESULTS:Results demonstrated a significant increase in mean sensitivity (MS, p = 0.0006) and a better perception of dimmer stimuli (p = 0.0004), indicating higher sensitivity. Results from individual eyes showed consistent improvements in retinal sensitivity and fixation stability. These findings were consistent with improvements in daily functioning-particularly in low-light conditions-reported by the patients during medical history assessment during the routine visits. CONCLUSION:Overall, the findings suggest that microperimetry could be an useful tool for monitoring functional outcomes after gene therapy.
PURPOSE:To characterize outpatient pediatric hereditary optic neuropathies in the United Arab Emirates. METHODS:Retrospective case series (2016-2023, inclusive). RESULTS:Thirteen probands were identified (nine males). Thirty-eight percent (5/13) had extraocular symptoms at the time of presentation (e.g. hearing loss or developmental delay). For the remaining 62% (8/13) who reported only visual symptoms at presentation, half (4/8) were subsequently diagnosed with extraocular findings (e.g. hearing loss or neurological regression). The single most common genetic diagnosis was heterozygous OPA1 variant (31%, 4/13). The remaining 69% (9/13) harbored pathogenic variants in nine different genes that were monoallelic (ATP1A3, NR2F1, PTCH1) or biallelic (ACO2, BTD, GALC, OPA1, WFS1, POLR3B). For these nine cases, two had treatable metabolic disease that had not been previously recognized before the presentation for visual loss (BTD, GALC). No pathogenic variant was recurrent in the series. DISCUSSION:Although private heterozygous OPA1 variant (dominant optic atrophy) was the single most frequent genotype in this cohort, non-OPA1-related cases were more common, genetically heterogenous, and often autosomal recessive. Children with hereditary optic neuropathy should be evaluated for actionable extraocular features such as hearing loss and undiagnosed metabolic disease as they are not infrequent and best addressed at an earlier age.
PURPOSE:To provide the first comprehensive, overview of the Danish Family Archive for Genetic Eye Diseases, a national umbrella registry on inherited eye disorders initiated in 1985. METHODS:A cross-sectional extraction of entries collected over 40 years was performed on 1 May 2025. Core variables included family identifier, clinical diagnosis, and genetic results. Descriptive statistics were generated within a secure registry environment. RESULTS:The registry contained 10,377 affected individuals from 3,412 unique families. Seventy-four distinct clinical diagnoses were documented; retinitis pigmentosa (1,709 cases) was the most frequent, followed by congenital cataract (1,220), autosomal dominant optic atrophy (1,077), congenital stationary night blindness (649) and Stargardt disease (555). Genetic data revealed 260 different disease-associated genes, the most prevalent being OPA1 (318 cases), ABCA4 (276), and USH2A (150). A confirmed genetic etiology was established for 2 972 individuals (28.6%) and in 2,052 families (60.9%). Syndromic involvement was recorded in 13%. CONCLUSIONS:The Danish Family Archive offers an unparalleled, nationwide overview of inherited eye disorders, confirming substantial diagnostic and genotypic heterogeneities. The registry data already accelerate clinical work-up and precision genetic counseling and enable rapid identification of well phenotyped and genotyped candidates for emerging therapies and clinical trials.
PURPOSE:To report foveal hypoplasia and high myopia in siblings who harbored biallelic pathogenic variants in the gene LOXL3 (lysyl oxidase-like 3; biallelic) and highlight LOXL3 as a candidate gene for this phenotype. METHOD:Retrospective case series. RESULTS:Two siblings, a 12-year-old boy and his 2-year-old sister, had foveal hypoplasia in the setting of high myopia. Whole exome sequencing revealed both to be homozygous for NM_032603.5: LOXL3 (lysyl oxidase-like 3) c.1036C>T; p.Arg346Trp and NM_000315.4: PTH (parathyroid hormone) c.128 G>A; p.Gly43Glu. The LOXL3 variant has previously been associated with Stickler syndrome; however, phenotypic reassessment did not reveal hearing loss, flat facies, palatal or skeletal abnormalities, or the vitreous phenotype of classic Stickler syndrome. The PTH variant was consistent with pseudohypoparathyroidism. The boy had been previously diagnosed with this by an endocrinologist, and phenotypic reassessment confirmed the same diagnosis in his sister. CONCLUSIONS:Biallelic LOXL3 pathogenic variants should be considered in the differential diagnosis of foveal hypoplasia with high myopia.
INTRODUCTION:Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is a rare inherited retinal disorder that often has delayed diagnosis due to overlapping features of intraocular inflammation, retinal degeneration, and retinal neovascularization. CASE PRESENTATION:We report a case of a 53-year-old male who presented with progressive panuveitis, peripheral visual field loss, and nyctalopia. Multimodal imaging demonstrated peripheral retinal nonperfusion, vascular leakage, cystoid macular edema, and progressive tractional vitreoretinal changes. Family history was notable for presumed age-related macular degeneration in the patient's father, later found on postmortem evaluation to have features suggestive of ADNIV. To determine the etiology of the clinical presentation, the patient underwent genetic testing using a targeted long-read sequencing inherited retinal disease panel, which identified a heterozygous missense variant in CAPN5, c.728G>A (p.Arg243His). DISCUSSION:The overlapping features of intraocular inflammation, retinal degeneration, and vasoproliferative disease frequently lead to delayed or incorrect diagnosis of ADNIV. The potentially causative variant identified has not been reported to cause disease before, but at that amino acid residue, a different missense variant has been identified as the causative variant in ADNIV patients as it localizes to a calcium-sensitive regulatory region adjacent to the catalytic domain, supporting a gain-of-function mechanism. Although currently classified as a variant of uncertain significance, its genomic context, rarity, and biologic plausibility support pathogenicity. CONCLUSIONS:This case expands the mutational spectrum of CAPN5-associated ADNIV and highlights the importance of integrating detailed clinical phenotyping with biologically informed genetic interpretation in complex inherited retinal disorders.
INTRODUCTION:Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder caused by mutations in IDUA, resulting in ⍺-L-iduronidase loss of function and glycosaminoglycan accumulation. Corneal clouding is the most consistent ocular manifestation and often prompts diagnostic evaluation. Retinal degeneration associated with MPS I has also been reported. The extent to which corneal clouding may be absent in MPS I, particularly in late adulthood, remains incompletely characterized. METHODS:Case report. RESULTS:We report a 71-year-old woman referred for longstanding pigmentary retinopathy with a history of early-onset aortic stenosis. Ophthalmologic examination demonstrated clear corneas bilaterally without evidence of corneal clouding. Multimodal retinal imaging revealed widespread pigmentary changes and retinal thinning, and full-field electroretinography showed markedly reduced rod responses, electronegative mixed responses, reduced cone and flicker responses, and reduced cone bipolar ON/OFF responses. Whole exome sequencing identified compound heterozygous IDUA variants c.1205G>A (p.W402*) and c.536C>T (p.T179M), supporting a diagnosis of MPS I. DISCUSSION:This case illustrates an unusually attenuated MPS I presentation characterized by very late diagnosis, absence of corneal clouding, and retina-predominant ocular involvement. These findings expand the recognized phenotypic spectrum of MPS I and highlight the importance of considering lysosomal storage disorders in patients with syndromic or atypical retinal degeneration, even in older adults.
PURPOSE:To describe the ocular and extraocular findings in two unrelated Turkish families with type 1 Stickler syndrome carrying two novel truncating COL2A1 variants and to emphasize the marked intrafamilial phenotypic variability. METHODS:Seven affected individuals from the two families underwent detailed ophthalmic examination including BCVA, slit-lamp biomicroscopy with vitreous phenotype assessment, fundus evaluation, and multimodal retinal imaging. Systemic evaluation included craniofacial, pediatric, orthopedic, and audiological assessments. Index cases underwent clinical exome sequencing; targeted NGS confirmed segregation in family members. Variants were classified as per ACMG criteria. RESULTS:In Family 1, a novel nonsense COL2A1 variant, c.3910C>T (p.Gln1304Ter), was identified as the father and three sons. Ocular findings ranged from mild myopia and epiretinal membranes to bilateral retinal detachment and macular holes. The membranous vitreous anomaly of type 1 Stickler syndrome was present in all; one child had Pierre Robin sequence and another had cleft palate. In Family 2, a novel nonsense COL2A1 variant, c.3016A>T (p.Lys1006Ter), was detected in the proband along with her mother and brother. The proband had rhegmatogenous retinal detachment; affected relatives showed milder phenotypes including isolated high myopia and high myopia with retinal detachment. Marked intrafamilial phenotypic variability was observed in both families. CONCLUSIONS:These two novel truncating COL2A1 variants expand the mutational spectrum of type 1 Stickler syndrome. This case series illustrates the broad clinical variability of the disease, from isolated high myopia to severe vitreoretinal complications, and supports early molecular diagnosis, family screening, and preventive ophthalmic surveillance.
Two cases of macular neovascularization (MNV) in female patients with genetically confirmed Gyrate Atrophy of the choroid and retina (GACR) are presented. Both patients experienced sudden central vision loss, with subfoveal MNV confirmed on multimodal imaging including optical coherence tomography angiography. The first patient showed improvement in best-corrected visual acuity (BCVA) from 20/60 to 20/30 following three monthly intravitreal anti-VEGF injections, followed by a treat-and-extend regimen. The second patient experienced five MNV recurrences over a five-year period, each managed with anti-VEGF therapy, achieving long-term visual stability at 20/40. Persistent subretinal fibrosis developed in both cases. These cases represent the first reported instance of recurrent MNV in GACR. A review of clinical findings and existing literature suggests that the pathogenesis may involve both GACR-associated retinal pigment epithelial dysfunction and high myopia. Anti-VEGF therapy proved effective in preserving vision, but the recurrent nature of MNV highlights the necessity of long-term follow-up. This report provides novel insight into a rare but vision-threatening complication of GACR and underscores the importance of early detection, treatment, and continued monitoring in affected patients.
PURPOSE:To evaluate retinal and choroidal microvascular alterations in patients with Familial Mediterranean Fever (FMF) and to investigate their associations with MEFV genotype and clinical phenotype using optical coherence tomography angiography (OCTA). METHODS:In this cross-sectional study, 130 FMF patients (260 eyes) and 120 age- and sex-matched healthy controls (240 eyes) underwent OCTA imaging. Patients were stratified according to MEFV genotype and clinical phenotype, including amyloidosis, arthritis, serositis, and erysipelas-like erythema. Vessel density parameters in the superficial and deep capillary plexus (SCP and DCP), foveal avascular zone (FAZ), retinal nerve fiber layer (RNFL), choriocapillaris flow area, and optic nerve head parameters were analyzed using linear mixed-effects models adjusted for age and sex. RESULTS:Compared with controls, FMF patients demonstrated significantly reduced DCP vessel density in the whole image, parafoveal, and perifoveal regions, whereas SCP, FAZ, RNFL, and optic nerve head parameters were comparable. Within the FMF cohort, age was the strongest predictor of reduced DCP vessel density and choriocapillaris flow. M694V carriage and amyloidosis were independently associated with lower parafoveal and perifoveal DCP vessel density. CONCLUSIONS:FMF is associated with selective deep retinal microvascular impairment, particularly in patients carrying the M694V mutation and in those with amyloidosis. OCTA-derived DCP parameters may serve as non-invasive biomarkers of systemic microvascular involvement in FMF.
