BACKGROUND: Occult Macular Dystrophy (OMD), primarily caused by retinitis pigmentosa 1-like 1 (RP1L1) variants, is a complex retinal disease characterised by progressive vision loss and a normal fundus appearance. This study aims to investigate the diverse phenotypic expressions and genotypic correlations of OMD in Chinese patients, including a rare case of Vitelliform Macular Dystrophy (VMD) associated with RP1L1.
METHODS: We analysed seven OMD patients and one VMD patient, all with heterozygous pathogenic RP1L1 variants. Clinical assessments included Best Corrected Visual Acuity (BCVA), visual field testing, Spectral Domain Optical Coherence Tomography (SD-OCT), multifocal Electroretinograms (mfERGs), and microperimetry. Next-generation sequencing was utilised for genetic analysis.
RESULTS: The OMD patients displayed a range of phenotypic variability. Most (5 out of 7) had the RP1L1 variant c.133 C > T; p.R45W, associated with central vision loss and specific patterns in SD-OCT and mfERG. Two patients exhibited different RP1L1 variants (c.3599G > T; p.G1200V and c.2880G > C; p.W960C), presenting milder phenotypes. SD-OCT revealed photoreceptor layer changes, with most patients showing decreased mfERG responses in the central rings. Interestingly, a unique case of VMD linked to the RP1L1 variant was observed, distinct from traditional OMD presentations.
CONCLUSIONS: This study highlights the phenotypic diversity within OMD and the broader spectrum of RP1L1-associated macular dystrophies, including a novel association with VMD. The findings emphasise the complexity of RP1L1 variants in determining clinical manifestations, underscoring the need for comprehensive genetic and clinical evaluations in macular dystrophies.

Adult-onset foveomacular vitelliform dystrophy (AOFVD) is a rare disease characterized by accumulation of yellowish deposits in the macula. Rarely, it may be complicated by choroidal neovascularization (CNV). Cases with CNV may be confused with occult CNV in age-related macular degeneration. In our case, we will present the visual and anatomical results of a patient with AOVF-related CNV, in which we administered 3 doses of intravitreal ranibizumab (IVR). A 59-year-old female patient, who attended our clinic with the complaint of decreased vision in both eyes, was diagnosed with AOVF-related CNV in both eyes and was treated with 3 doses of IVR for 3 months. Despite the improvement in visual and anatomical functions 1 month after the first dose, vision decreased, and anatomical functions regressed to the pre-injection state in continued injections. IVR therapy is not an appropriate treatment option in the treatment of AOVF-associated CNV.

OBJECTIVE: To explore clinical risk factors and OCT features associated with worse visual acuity (VA), progression of disease, choroidal neovascularization (CNV), and atrophy in eyes with adult-onset foveomacular vitelliform dystrophy (AOFVD).
METHODS: Single-center, retrospective, observational cohort study.
METHODS: Patients seen at Duke Eye Center between January 2012 and May 2023 with a diagnosis of AOFVD confirmed via OCT and fundus autofluorescence.
METHODS: Baseline and final-visit images from eyes with AOFVD were examined. Disease stage was assigned, and presence of atrophy or CNV was determined. Clinical and OCT features associated with progression to atrophy and CNV were determined using t tests and chi-square analysis. Correlation with lower VA was determined using linear regression.
METHODS: Association of clinical characteristics and OCT features with worse VA, progression of disease, CNV, and atrophy as determined by independent t tests, chi-square analysis, and linear regression (P < 0.05).
RESULTS: One hundred one eyes (63 patients) met inclusion criteria for this study, with mean follow-up duration of 48 months (standard deviation, 31 months). Fifty-one percent of eyes progressed beyond baseline staging during follow-up; among baseline stage 1 eyes, incidence of atrophy was 0.068/person-year; incidence of CNV was 0.022/person-year. Risk factors for worse final VA were baseline presence of vitreomacular traction ([VMT], P = 0.006), ellipsoid zone attenuation (P = 0.02), and increased lesion height and width (P < 0.001). Predictors of progression include diabetes mellitus (P = 0.01), statin use (P = 0.03), presence of hyperreflective foci (P = 0.01), and increased lesion width and volume (P = 0.03 and P = 0.04, respectively). Predictors of atrophy include the baseline presence of VMT (P = 0.02), decreased choroidal thickness (P = 0.03), and greater maximal height, width, and volume of the lesion (P = 0.03, P = 0.02, and P = 0.009, respectively). Lower baseline VA (P = 0.03) and increased lesion volume (P = 0.04) were associated with CNV.
CONCLUSIONS: Clinical and OCT imaging features at baseline may prove useful in stratifying patient risk for progression, atrophy, CNV, and worse VA. Features such as statin use, diabetes, baseline VA, and laterality should be accounted for. OCT features, such as lesion size, VMT, ellipsoid zone attenuation, choroidal thickness, and hyperreflective foci, may impart greater risk of poor outcomes. Future prospective analysis accounting for the time to development of atrophy and CNV is needed.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

UNASSIGNED: To review all reported disease-causing mutations in BEST1, perform genotype-phenotype correlation, and estimate disease prevalence in the Israeli population.
UNASSIGNED: Medical records of patients diagnosed with Best disease and allied diseases from nine Israeli medical centers over the past 20 years were collected, as were clinical data including ocular findings, electrophysiology results, and retina imaging. Mutation detection involved mainly whole exome sequencing and candidate gene analysis. Demographic data were obtained from the Israeli Bureau of Statistics (January 2023). A bibliometric study was also conducted to gather mutation data from online sources.
UNASSIGNED: A total of 134 patients were clinically diagnosed with Best disease and related conditions. The estimated prevalence of Best disease was calculated to be 1 in 127,000, with higher rates among Arab Muslims (1 in 76,000) than Jews (1 in 145,000). Genetic causes were identified in 76 individuals (57%), primarily showing autosomal-dominant inheritance due to BEST1 mutations (58 patients). Critical conserved domains were identified consisting of a high percentage of dominant missense mutations, primarily in transmembrane domains and the intracellular region (Ca2+ binding domain) of the BEST1 protein.
UNASSIGNED: This study represents the largest cohort of patients with Best disease reported in Israel and globally. The prevalence in Israel is akin to that in Denmark but is lower than that in the United States. Critical conserved domains within the BEST1 protein are pivotal for normal functioning, and even minor missense alterations in these areas lead to a dominant disease manifestation. Genetic testing is indispensable as the gold standard for Best disease diagnosis due to the variable clinical presentation of the disease.

OBJECTIVE: To analyze the genetic findings, clinical spectrum, and natural history of Best vitelliform macular dystrophy (BVMD) in a cohort of 222 children and adults.
METHODS: Single-center retrospective, consecutive, observational study.
METHODS: Patients with a clinical diagnosis of BVMD from pedigrees with a likely disease-causing monoallelic sequence variant in the BEST1 gene.
METHODS: Data were extracted from electronic and physical case notes. Electrophysiologic assessment and molecular genetic testing were analyzed.
METHODS: Molecular genetic test findings and clinical findings including best-corrected visual acuity (BCVA), choroidal neovascularization (CNV) rates, and electrophysiologic parameters.
RESULTS: Two hundred twenty-two patients from 141 families were identified harboring 69 BEST1 variants. Mean age at presentation was 26.8 years (range, 1.3-84.8 years) and most patients (61.5%) demonstrated deterioration of central vision. Major funduscopic findings included 128 eyes (30.6%) with yellow vitelliform lesions, 78 eyes (18.7%) with atrophic changes, 49 eyes (11.7%) with fibrotic changes, 48 eyes (11.5%) with mild pigmentary changes, and 43 eyes (10.3%) showing a vitelliruptive appearance. Mean BCVA was 0.37 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/47) for the right eye and 0.33 logMAR (Snellen equivalent, 20/43) for the left eye at presentation, with a mean annual loss rate of 0.013 logMAR and 0.009 logMAR, respectively, over a mean follow-up of 9.7 years. Thirty-seven patients (17.3%) received a diagnosis of CNV over a mean follow-up of 8.0 years. Eyes with CNV that received treatment with an anti-vascular endothelial growth factor (VEGF) agent showed better mean BCVA compared with eyes that were not treated with an anti-VEGF agent (0.28 logMAR [Snellen equivalent, 20/38] vs. 0.62 logMAR [Snellen equivalent, 20/83]). Most eyes exhibited a hyperopic refractive error (78.7%), and 13 patients (6.1%) received a diagnosis of amblyopia. Among the 3 most common variants, p.(Ala243Val) was associated with a later age of onset, better age-adjusted BCVA, and less advanced Gass stages compared with p.(Arg218Cys) and p.(Arg218His).
CONCLUSIONS: BVMD shows a wide spectrum of phenotypic variability. The disease is very slowly progressive, and the observed phenotype-genotype correlations allow for more accurate prognostication and counselling.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Acute exudative polymorphous vitelliform maculopathy (AEPVM) is a rare entity characterized by acute multifocal macular detachment with polymorphous subretinal vitelliform deposits. The disease is a presumed retinal pigment epithelial dysfunction and is reported to occur with malignancies. We report a case of a 32-year-old otherwise healthy woman who presented with an acute bilateral visual disturbance a few days after testing positive for coronavirus disease 2019 (COVID-19). Her initial visual acuity was 6/6 in both eyes. Fundus examination revealed bilateral multifocal round yellowish subretinal deposits. Spectral-domain optical coherence tomography showed bilateral foveal serous retinal detachment with subretinal hyperreflective materials consistent with vitelliform deposits. Systemic workup to exclude malignancies and genetic diseases was unremarkable. The patient was observed without treatment, and the vitelliform materials gradually resolved over 18 months of follow-up. In our era of the global pandemic, AEPVM may be associated with COVID-19 infection.

The present study aimed to compare retinal sensitivity (RS) at each stage and to evaluate the relationship between RS and fundus autofluorescence (FAF) pattern in adult-onset foveomacular vitelliform dystrophy (AOFVD). We retrospectively reviewed 17 eyes of 13 patients with AOFVD. In addition to best-corrected visual acuity (VA), RS within the affected lesion and optical coherence tomography (OCT) measurements were carried out in each participant. All the examined eyes were classified into 4 stages and 3 FAF patterns. RS was superimposed on OCT fundus image and RS within the affected lesion was calculated in each eye. The relationships between visual functions (VA and RS within the affected lesion) and stages and also FAF patterns were analyzed using the linear mixed model. As a result, RS within the affected lesion was significantly associated with FAF pattern, but not with stage. In contrast, VA was correlated with neither stages nor FAF patterns. Our current result suggested that RS within the affected lesion was related to FAF patterns but this was not the case with VA in eyes with AOFVD, demonstrating the usefulness of measuring RS, not only VA, to comprehend the disease status in AOFVD.

OBJECTIVE: To study retinal microvascular parameters in patients with butterfly-shaped pattern dystrophy (BPD) and adult foveomacular vitelliform dystrophy (AFVD).
METHODS: This case-control study included BPD and AFVD patients in a tertiary university hospital. Eyes with known ocular disease and prior ocular surgery other than uncomplicated cataract surgery were excluded. Right eyes of healthy individuals without systemic or ocular disease were included as controls. En face 6×6mm angiograms were obtained with the RTVue XR Avanti (Optovue, USA). We used the Kruskal-Wallis test to compare vessel density (VD) values of the retina, optic disc and foveal avascular zone (FAZ) between groups. Dunn-Bonferroni correction was used for pairwise comparisons.
RESULTS: Eighteen eyes of 10 BPD patients, 17 eyes of 9 AFVD patients, and 26 right eyes of 26 controls were included. Six patients in the BPD, 4 patients in the AFVD, and 16 patients in the control group were female. The groups did not differ by sex (P=0.650). AFVD patients were of higher mean age (64.3±7.8) than BPD patients (55.9±11.1) and controls (53.6±5.5) (P=0.008, p=0.009). In BPD (P=0.008, P=0.044) and AFVD (P=0.006, P=0.002), parafoveal and perifoveal vessel density (VD) of the superficial capillary plexus were lower than controls. Parafoveal VD of the deep capillary plexus in AFVD was lower than in controls (P=0.012). There was no difference in the foveal avascular area between groups (P=0.563). Optic discs parameters did not differ.
CONCLUSIONS: A comparable loss in vascular density may indicate shared pathophysiology or represent a common sign of impairment in retinal homeostasis. Further research is needed to clarify underlying microvascular pathogenetic mechanisms in pattern dystrophies.

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A precise, Eco-friendly, and highly sensitive RP-HPLC method was employed using quality-by-design principles to concurrently identify cephalexin and cefixime residues in the manufacturing machines using a hypersil BDS C18 column (250 × 4.6 mm, 5 μm) at wavelength 254 nm. The Box-Behnken design was applied to obtain the best chromatographic conditions with the fewest possible trials. Three independent factors viz organic composition, flow rate, and pH were used to assess their effects on the responses\' resolution and retention time. Overlay plot and desirability functions were implemented to predict responses of the high resolution and relatively short retention time using a mobile phase composed of acidic water: acetonitrile (85:15, v/v) at pH 4.5 adjusted by phosphoric acid with a flow rate of 2.0 mL/min. The spectral overlapping of the drugs was successfully resolved by the mean centering ratio (MCR) spectra approach at 261 nm and 298 nm for cephalexin and cefixime, respectively. Good linearity results were obtained for the suggested HPLC and MCR methods over the concentration range of (0.05-10 ppm) and (5-30 ppm) with a detection limit of 0.003, 0.004, 0.26, and 0.23 ppm, and quantitation limits of 0.008, 0.013, 0.79, and 0.68 ppm for cephalexin and cefixime, respectively, with a correlation coefficient of ≥ 0.9998 and good swab recovery results of 99-99.5%. A process capability index was accomplished for chemical and micro results, illustrating that both are extremely capable. The suggested method was effectively validated using ICH recommendations.