Macular Dystrophy Research Articles

Multimodal Retinal Imaging and Microperimetry Reveal a Novel Phenotype and Potential Trial End Points in CRB1-Associated Retinopathies.

PurposeBiallelic crumbs cell polarity complex component 1 (CRB1) mutations can present as Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), or cystic maculopathy. This study reports a novel phenotype of asymptomatic fenestrated slit maculopathy (AFSM) and examines macular volume profile and microperimetry as clinical trial end points in CRB1-associated retinopathies.MethodsTwelve patients from nine families with CRB1 mutation were recruited. Ultra-widefield (UWF) color fundus photography and autofluorescence (AF), spectral-domain optical coherence tomography (SD-OCT), microperimetry, and adaptive optics (AO) imaging were performed. Macular volume profiles were compared with age-matched healthy controls. Genotyping was performed using APEX genotyping microarrays, targeted next-generation sequencing, and Sanger sequencing.ResultsWe identified one patient with LCA, five patients with RP, and four patients with macular dystrophy (MD) with biallelic CRB1 mutations. Two siblings with compound heterozygote genotype (c.[2843G>A]; [498_506del]) had AFSM characterized by localized outer retinal disruption on SD-OCT and parafoveal cone loss on AO imaging despite normal fundus appearance, visual acuity, and foveal sensitivity. UWF AF demonstrated preserved para-arteriolar retinal pigment epithelium (PPRPE) in all patients with RP. Microperimetry documented preserved central retinal function in six patients. The ratio of perifoveal-to-foveal retinal volume was greater than controls in 89% (8/9) of patients with RP or MD, whereas central subfield and total macular volume were outside normal limits in 67% (6/9).ConclusionsAO imaging was helpful in detecting parafoveal cone loss in asymptomatic patients. Macular volume profile and microperimetry parameters may have utility as CRB1 trials end points.Translational RelevanceMacular volume and sensitivity can be used as structural and functional end points for trials on CRB1-associated RP and MD.

Retinal Oxygenation in Inherited Diseases of the Retina.

(1) Background: The aim of our study was to investigate the relationship between retinal metabolic alterations (retinal vessel oximetry, RO) and structural findings (retinal vessel diameter, central retinal thickness and retinal nerve fiber layer thickness, RNFL) in patients with inherited retinal diseases (IRDs). (2) Methods: A total of 181 eyes of 92 subjects were examined: 121 eyes of 62 patients with IRDs were compared to 60 eyes of 30 healthy age-matched controls. The retinal vessel oximetry was performed with the oxygen saturation measurement tool of the Retinal Vessel Analyser (RVA; IMEDOS Systems UG, Jena, Germany). The oxygen saturation in all four major peripapillary retinal arterioles (A-SO2; %) and venules (V-SO2; %) were measured and their difference (A-V SO2; %) was calculated. Additionally, retinal vessel diameters of the corresponding arterioles (D-A; µm) and venules (D-V; µm) were determined. The peripapillary central retinal thickness and the RNFL thickness were measured using spectral domain optical coherence tomography (SD-OCT) (Carl Zeiss Meditec, Dublin, CA, USA). Moreover, we calculated the mean central retinal oxygen exposure (cO2-E; %/µm) and the mean peripapillary oxygen exposure (pO2-E; %/µm) per micron of central retinal thickness and nerve fiber layer thickness by dividing the mean central retinal thickness (CRT) and the RNFL thickness with the mean A-V SO2. (3) Results: Rod-cone dystrophy patients had the highest V-SO2 and A-SO2, the lowest A-V SO2, the narrowest D-A and D-V and the thickest RNFL, when compared not only to controls (p ≤ 0.040), but also to patients with other IRDs. Furthermore, in rod-cone dystrophies the cO2-E and the pO2-E were higher in comparison to controls and to patients with other IRDs (p ≤ 0.005). Cone-rod dystrophy patients had the lowest cO2-E compared to controls and patients with other IRDs (p ≤ 0.035). Evaluated in central zones, the cO2-E was significantly different when comparing cone-rod dystrophy (CRD) against rod-cone dystrophy (RCD) patients in all zones (p < 0.001), whereas compared with controls and patients with inherited macular dystrophy this was observed only in zones 1 and 2 (p ≤ 0.018). The oxygen exposure was also the highest in the RCD group for both the nasal and the temporal peripapillary area, among all the evaluated groups (p ≤ 0.025). (4) Conclusions: The presented metabolic-structural approach enhances our understanding of inherited photoreceptor degenerations. Clearly demonstrated through the O2-E comparisons, the central and the peripapillary retina in rod-cone dystrophy eyes consume less oxygen than the control-eyes and eyes with other IRDs. Rod-cone dystrophy eyes seem to be proportionally more exposed to oxygen, the later presumably leading to more pronounced oxidative damage-related remodeling.

CRB1-associated retinal dystrophies in a Belgian cohort: genetic characteristics and long-term clinical follow-up

AimTo investigate the natural history in a Belgian cohort of CRB1-associated retinal dystrophies.MethodsAn in-depth retrospective study focusing on visual function and retinal structure.ResultsForty patients from 35 families were included (ages:...

Clinically-identified C-terminal mutations in fibulin-3 are prone to misfolding and destabilization

Distinct mutations in the secreted extracellular matrix protein, fibulin-3 (F3), have been associated with a number of ocular diseases ranging from primary open angle glaucoma to cuticular age-related macular degeneration to a rare macular dystrophy, Malattia Leventinese (ML). The R345W F3 mutation that causes ML leads to F3 misfolding, inefficient secretion and accumulation at higher intracellular steady state levels in cultured cells. Herein, we determined whether fifteen other clinically-identified F3 mutations also led to similar levels of misfolding and secretion defects, which might provide insight into their potential pathogenicity. Surprisingly, we found that only a single F3 variant, L451F, presented with a significant secretion defect (69.5 ± 2.4% of wild-type (WT) F3 levels) and a corresponding increase in intracellular levels (226.8 ± 25.4% of WT F3 levels). Upon follow-up studies, when this conserved residue (L451) was mutated to a charged (Asp or Arg) or bulky (Pro, Trp, Tyr) residue, F3 secretion was also compromised, indicating the importance of small side chains (Leu, Ala, or Gly) at this residue. To uncover potential inherent F3 instability not easily observed under typical culture conditions, we genetically eliminated the sole stabilizing N-linked glycosylation site (N249) from select clinically-identified F3 mutants. This removal exacerbated R345W and L451F secretion defects (19.8 ± 3.0% and 12.4 ± 1.2% of WT F3 levels, respectively), but also revealed a previously undiscovered secretion defect in another C-terminal variant, Y397H (42.0 ± 10.1% of WT F3 levels). Yet, glycan removal did not change the relative secretion of the N-terminal mutants tested (D49A, R140W, I220F). These results highlight the uniqueness and molecular similarities between the R345W and L451F variants and also suggest that previously identified disease-associated mutations (e.g., R140W) are indistinguishable from WT with respect to secretion, hinting that they may lead to disease by an alternative mechanism.

Defining inclusion criteria and endpoints for clinical trials: a prospective cross-sectional study in CRB1-associated retinal dystrophies.

PurposeTo investigate the retinal structure and function in patients with CRB1‐associated retinal dystrophies (RD) and to explore potential clinical endpoints.MethodsIn this prospective cross‐sectional study, 22 patients with genetically confirmed CRB1‐RD (aged 6–74 years), and who had a decimal best‐corrected visual acuity (BCVA) ≥ 0.05 at the last visit, were studied clinically with ETDRS BCVA, corneal topography, spectral‐domain optical coherence tomography (SD‐OCT), fundus autofluorescence, Goldmann visual field (VF), microperimetry, full‐field electroretinography (ERG) and full‐field stimulus testing (FST). Ten patients were from a genetic isolate (GI).ResultsPatients had retinitis pigmentosa (n = 19; GI and non‐GI), cone‐rod dystrophy (n = 2; GI) or macular dystrophy (n = 1; non‐GI). Median age at first symptom onset was 3 years (range 0.8–49). Median decimal BCVA in the better and worse‐seeing eye was 0.18 (range 0.05–0.83) and 0.08 (range light perception‐0.72), respectively. Spectral‐domain optical coherence tomography (SD‐OCT) showed cystoid maculopathy in 8 subjects; inner retinal thickening (n = 20), a well‐preserved (para)foveal outer retina (n = 7) or severe (para)foveal outer retinal atrophy (n = 14). All retinal layers were discernible in 13/21 patients (62%), with mild to moderate laminar disorganization in the others. Nanophthalmos was observed in 8 patients (36%). Full‐field stimulus testing (FST) provided a subjective outcome measure for retinal sensitivity in eyes with (nearly) extinguished ERG amplitudes.ConclusionsDespite the generally severe course of CRB1‐RDs, symptom onset and central visual function are variable, even at advanced ages. Phenotypes may vary within the same family. Imaging and functional studies in a prospective longitudinal setting should clarify which endpoints may be most appropriate in a clinical trial.

Customized Slab-Segmentation Method for Projection-Artifact Elimination in Best Vitelliform Macular Dystrophy: A Swept-Source Optical Coherence Tomography Angiography Study

PurposeTo assess the efficacy of customized slab segmentation in eliminating projection artifacts in swept-source optical coherence tomography angiography (SS-OCTA) images of Best vitelliform macular dystrophy (BVMD).MethodsProspective case series including different stages of BVMD. We analyzed SS-OCTA images for flow signals in the outer retina and coregistered B-scan images for distortion of the segmentation slabs defining the outer retina. We applied a customized method for slab realignment whenever BVMD lesions produced distortion of the slabs. Afterward, we checked the images to determine whether the previously noted flow signal had persisted or disappeared, described as “true flow” or “pseudoflow”, respectively. Categorical variables were analyzed with X2 or Fisher’s exact tests, while quantitative variables were analyzed with independent t-test at p<0.05.ResultsThe study included 39 eyes of 22 patients. We detected BVMD patterns I (dome-shaped hyperreflective lesion without neurosensory retinal detachment), II (knob-like hyperreflective lesion with localized neurosensory retinal detachment), and III (heterogeneous scattered hyperreflective material) in 49%, 23%, and 28% of eyes, respectively. Pseudoflow was evident mostly in eyes with pattern II lesions, presence of flow signal within BVMD lesions, and lesions whose height represented >80% of the retinal thickness (p<0.001).ConclusionCustomized slab segmentation is effective in eliminating projection artifact in SS-OCTA images of BVMD.SummaryProjection artifact is a significant confounding factor in emerging SS-OCTA technology through production of pseudoflow signals that can lead to misinterpretation of images of BVMD lesions. The present study proposes a customized method for correction of segmentation errors to eliminate projection artifacts in SS-OCTA images of BVMD patients.

A novel phenotype in a family with autosomal dominant retinal dystrophy due to c.1430A > G in retinoid isomerohydrolase (RPE65) and c.37C > T in bestrophin 1 (BEST1).

The c.1430A > G (Asp477Gly) variant in RPE65 has been reported in Irish and Scottish families with either an autosomal dominant retinal dystrophy (adRD) that resembles choroideremia, a vitelliform macular dystrophy or an isolated macular atrophy. We report novel features on multimodal imaging and the natural history of a family harbouring this variant in combination with the BEST1 c.37C > T (Arg13Cys) variant. Members of a family with an adRD were examined clinically to ascertain phenotype and underwent genetic testing. Multimodal imaging included widefield colour fundus photography, quantitative autofluorescence (qAF) and spectral domain optical coherence tomography. Electrophysiology and microperimetry were also performed. Vision loss was attributed to foveal atrophy in the proband and choroidal neovascularisation and a vitello-eruptive lesion in one affected son. Peripheral retinal white dots corresponding to subretinal deposits were seen in three patients. The median qAF8 values in the proband (I:1) were low (40 and 101 in OD and OS) at age 79. Similarly, the qAF8 values for the middle son (II:2) were also low (100 and 87 in ODS and OS) at age 60. Electrophysiology showed disproportionate reduction in Arden ratio prior to the gradual loss of full-field responses. Microperimetry demonstrated an enlarging scotoma in the proband. The coexistence of the pathogenic BEST1 c.37C > T variant may modify clinical features observed in RPE65 adRD. This study expands our understanding of RPE65 adRD as a retinoid cycle disorder supported by the reduced qAF, fine white retinal dots and corresponding subretinal deposits on OCT in affected members.

Gene Therapy of Dominant CRX-Leber Congenital Amaurosis using Patient Stem Cell-Derived Retinal Organoids.

SummaryMutations in the photoreceptor transcription factor gene cone-rod homeobox (CRX) lead to distinct retinopathy phenotypes, including early-onset vision impairment in dominant Leber congenital amaurosis (LCA). Using induced pluripotent stem cells (iPSCs) from a patient with CRX-I138fs48 mutation, we established an in vitro model of CRX-LCA in retinal organoids that showed defective photoreceptor maturation by histology and gene profiling, with diminished expression of visual opsins. Adeno-associated virus (AAV)-mediated CRX gene augmentation therapy partially restored photoreceptor phenotype and expression of phototransduction-related genes as determined by single-cell RNA-sequencing. Retinal organoids derived from iPSCs of a second dominant CRX-LCA patient carrying K88N mutation revealed the loss of opsin expression as a common phenotype, which was alleviated by AAV-mediated augmentation of CRX. Our studies provide a proof-of-concept for developing gene therapy of dominant CRX-LCA and other CRX retinopathies.

Macular neovascularization in AMD, CSC and best vitelliform macular dystrophy: quantitative OCTA detects distinct clinical entities

BackgroundTo perform a quantitative optical coherence tomography (OCT) angiography (OCTA) analysis of macular neovascularization (MNV) secondary to age-related macular degeneration (AMD), central serous chorioretinopathy (CSC) and best vitelliform macular dystrophy (BVMD), with the aim of highlighting quantitative features indicating different clinical entities.MethodsStudy design: prospective, interventional. We recruited patients affected by AMD, CSC or BVMD, complicated by naive MNV. All patients underwent complete ophthalmologic examination and multimodal imaging. They were treated with anti-VEGF injections, following a pro-re-nata regimen. The ensuing follow-up lasted 1 year. Quantitative dye-based angiography, OCT, and OCTA parameters were analysed to obtain cutoff values able to distinguish two clinically different patient subgroups for each retinal disease. The main outcome measures were best-corrected visual acuity (BCVA), central macular thickness, vessel density of superficial, deep and choriocapillaris plexa, vessel tortuosity (VT) of MNV, vessel dispersion of MNV, number of injections, MNV/leakage ratio, MNV size, speckled fluorescence, and outer retinal atrophy.ResultsNinety-eight eyes affected by MNV (98 patients) were analysed. These included 66 eyes affected by AMD, 18 displaying CSC, and 14 eyes with BVMD. BCVA was alike in the three groups, both at baseline and after 1 year (p > 0.05). An MNV VT cutoff of 8.40 at baseline detected two patient subgroups differing significantly in terms of morpho-functional features, found both at baseline and at the end of the follow-up.ConclusionsQuantitative OCTA suggested that the MNV’s VT might be able to provide a better characterization of two different morpho-functional manifestations in AMD, CSC and BVMD.

Surgical Transplantation of Human RPE Stem Cell-Derived RPE Monolayers into Non-Human Primates with Immunosuppression.

SummaryRecent trials of retinal pigment epithelium (RPE) transplantation for the treatment of disorders such as age-related macular degeneration have been promising. However, limitations of existing strategies include the uncertain survival of RPE cells delivered by cell suspension and the inherent risk of uncontrolled cell proliferation in the vitreous cavity. Human RPE stem cell-derived RPE (hRPESC-RPE) transplantation can rescue vision in a rat model of retinal dystrophy and survive in the rabbit retina for at least 1 month. The present study placed hRPESC-RPE monolayers under the macula of a non-human primate model for 3 months. The transplant was able to recover in vivo and maintained healthy photoreceptors. Importantly, there was no evidence that subretinally transplanted monolayers underwent an epithelial-mesenchymal transition. Neither gliosis in adjacent retina nor epiretinal membranes were observed. These findings suggest that hRPESC-RPE monolayers are safe and may be a useful source for RPE cell replacement therapy.

Vitelliform Distrofiye Sekonder Koroidal Neovaskülarizasyon: Optik Koherens Tomografi Anjiyografi ve Fluoresein Anjiyografi Bulguları

This case series aims to interpret the findings of optical coherence tomography angiography (OCTA) and fluorescein angiography (FA) in detecting choroidal neovascularization (CNV) in juvenile Best vitelliform macular dystrophy (BVMD) and adult-onset foveomacular vitelliform dystrophy (AOFVD). Two patients with BVMD and one patient with AOFVD were evaluated, and color fundus photography, spectral-domain optical coherence tomography, FA, and OCTA were performed. In 4 of 6 eyes, OCTA revealed neovascular formations in the outer retina and choriocapillaris. It is an effective, non-invasive method for showing CNV formation using OCTA in BVMD and AOFVD, and it has aspects that are superior to FA.

Long-Term Maintenance of Vision and Resolution of Vitelliform Lesions with Systemic Phosphodiesterase 5/6 Treatment (Sildenafil)

BACKGROUND: Adult vitelliform macular dystrophy results in loss of central vision. The use of systemic sildenafil has been proven to increase choroidal blood flow. This is a report of a favorable long-term treatment outcome using systemic sildenafil for a patient with adult onset vitelliform macular dystrophy. CASE PRESENTATION: A 55-year-old woman presenting with bilateral subretinal vitelliform lesions was initially assessed by full-field electroretinogram, electro-oculogram and direct sequencing of the RDS/PRPH2 and BEST1 genes. Best-corrected visual acuity, spectral domain-optical coherence tomography and color fundus photography were obtained and analyzed over a 5-year treatment course which included bevacizumab (Avastin) injections in the right eye and left eye and subsequent ranibizumab (Lucentis) treatments in the left eye. Lipid resolution in the right eye was seen with bevacizumab after two months of treatment, while the left eye was unresponsive to eight subsequent injections of bevacizumab, followed by ranibizumab over a period of twenty months. Systemic sildenafil was started, off label, at 20 months following course of intravitreal injections. Following initiation of sildenafil, there were both measured and patient-reported improvements in the left eye following after two months of sildenafil. CONCLUSIONS: Systemic phosphodiesterase (PDE)-5 and -6 inhibitors may facilitate the removal of lipid and waste from the subretinal space by increasing perfusion in patients with vitelliform lesions and aid in maintaining and/or recovering photoreceptor function.

Treatment with a set of peptide bioregulators for age-related macular dystrophy

Treatment with a set of peptide bioregulators for age-related macular dystrophy

A novel variant of autosomal recessive best vitelliform macular dystrophy and management of early-onset complications

To report an adult with autosomal recessive Best vitelliform macular dystrophy with a new homozygous BEST1 mutation, the management of a cystoid macular edema with intravitreal aflibercept in the proband, and the findings in the parents, carriers of heterozygous BEST1 mutations. A 28-year-old female presented with blurry andreduced vision in her both eyes with bilateral vitelliform macular lesions. The patient's parents were also examined. Examinations included electrooculogram (EOGs), imaging studies, and BEST1 gene testing. Interventions included treatment with intravitreal aflibercept for both eyes. The patient presented with visual acuity of 20/20 OD 20/30 OS, RPE changes, multifocal subretinal yellowish deposits resembling vitelliform deposits and subretinal fluids. Cystoid macular edema developed after one month, causing vision reduction (20/28 OD 20/30 OS). Visual acuity recovered to 20/20 OU after serial intravitreal aflibercept injections. The proband showed subnormal EOG Arden ratios. Molecular testing showed the homozygous missense variant c.695T>G p. (IIe232Ser) In exon 6 of the BEST1 mutations and to the best of our knowledge, this variant, which was confirmed by conventional Sanger sequencing, has neither been annotated in databases nor been described in the literature so for (Human Genome Molecular Database 2018.1). In the heterozygous parents, EOGs were subnormal, and minimal autofluorescence changes were seen.Clinical Relevance:Prompt recognition and treatment of cystoid macular edema management effectively restore vision. Awareness and recognition of recessive inheritance permit correct diagnosis and counseling.

Clinical and electroretinographic profile of 27 patients with Stargardt disease treated at a hospital in Brazil.

Stargardt disease is the most common type of juvenile-onset macular dystrophy. It is bilateral and symmetrical in appearance, affects the macula, and its main characteristic is the loss of central vision that starts in the first or second decade of life. The purpose of this study was to describe the profile of the patients evaluated at the Complexo Hospital de Clínicas da Universidade Federal do Paraná, as well as describe the electroretinographic findings with the full-field electroretinogram in these patients. An observational, retrospective study was performed by analysis of records and electroretinographic examinations of 27 patients with Stargardt disease and fundus flavimaculatus who were treated at the Complexo Hospital de Clínicas da Universidade Federal do Paraná's Department of Ocular Electrophysiology and Neuro-Ophthalmology between 1997 and 2014. The patients included in this study presented clinical features, fundus examination and/or electroretinographic findings compatible with Stargardt disease. The visual acuity in the best eye varied from 0 to 1.6 logMAR (20/20 to 20/800) with an average of 0.89 ± 0.42 logMAR. The age at onset of symptoms varied from since birth to 36 years old (average 19.2 ± 9.2) with the majority of patients having symptom onset in the first or second decade of life. The mean time from the disease's first symptoms until the diagnosis was 7.3 years. In the fundus examination, every patient presented some kind of abnormality. In the electroretinogram analysis, the majority of patients had results that differed from those of sample controls, i.e., reduced amplitude and increased implicit time in the photopic and scotopic phases. The visual acuity and the age at symptoms onset in this study were compatible with the natural history of this dystrophy. The typical fundus appearance of Stargardt disease and altered electroretinogram were more frequent because of the delay until diagnosis. New prospective studies are necessary to evaluate these patients based on emergent technologies.

Maternally inherited diabetes and deafness (MIDD) syndrome with m.3243A&gt;G mutation associated with renal failure — a case report

Maternally-inherited diabetes with deafness (MIDD) is a rare form of monogenic diabetes that results, in most cases, from an A-to-G transition at position 3243 of mitochondrial DNA (m.3243A>G). The clinical presentation of m.3243A>G mutation is variable, ranging from mild to severe phenotypes. Diabetes is often accompanied by sensorineural deafness, cardiomyopathy, neuromuscular, psychiatric disorders, macular dystrophy and renal failure (kidney manifestations in adults presenting with this mutation remain poorly defined). The study presents a case of a 40-years-old woman with a history of bilateral sensorineural deafness, renal failure and diabetes that was diagnosed due to increasing muscle weakness during exercise. MIDD was diagnosed based on the clinical picture and the results of laboratory studies including genetic testing. As far as we know, glomerulopathy with incomplete distal renal tubular acidosis has never been described before as a cause of renal failure in MIDD patients.

AAV-CRB2 protects against vision loss in an inducible CRB1 retinitis pigmentosa mouse model

Loss of Crumbs homolog 1 (CRB1) or CRB2 proteins in Müller cells or photoreceptors in the mouse retina results in a CRB dose-dependent retinal phenotype. In this study, we present a novel Müller cell-specific Crb1KOCrb2LowMGC retinitis pigmentosa mouse model (complete loss of CRB1 and reduced levels of CRB2 specifically in Müller cells). The Crb double mutant mice showed deficits in electroretinography, optokinetic head tracking, and retinal morphology. Exposure of retinas to low levels of dl-α-aminoadipate acid induced gliosis and retinal disorganization in Crb1KOCrb2LowMGC retinas but not in wild-type or Crb1-deficient retinas. Crb1KOCrb2LowMGC mice showed a substantial decrease in inner/outer photoreceptor segment length and optokinetic head-tracking response. Intravitreal application of rAAV vectors expressing human CRB2 (hCRB2) in Müller cells of Crb1KOCrb2LowMGC mice subsequently exposed to low levels of dl-α-aminoadipate acid prevented loss of vision, whereas recombinant adeno-associated viral (rAAV) vectors expressing human CRB1 (hCRB1) did not. Both rAAV vectors partially protected the morphology of the retina. The results suggest that hCRB expression in Müller cells is vital for control of retinal cell adhesion at the outer limiting membrane, and that the rAAV-cytomegalovirus (CMV)-hCRB2 vector is more potent than rAAV-minimal CMV (CMVmin)-hCRB1 in protection against loss of vision.

Histomorphological study of corneal dystrophies

Introduction: The term Corneal Dystrophy refers to a rare heterogeneous group of genetically determined, bilateral, symmetric, primary diseases, restricted to cornea and not associated with previous ocular inflammation. The dystrophies are classified based on the layer of cornea involved, into superficial, stromal and posterior dystrophies, each of which is genetically determined. Though the clinical features are often characteristic, definitive diagnosis is possible only after histological examination. The management protocols and visual prognosis vary with the underlying conditions. The incidence of the subtypes varies with the geographic locations. Objective: To study the prevalence of various subtypes of Corneal Dystrophies in corneal button specimens obtained after penetrating keratoplasty in a referral ophthalmic institute and to correlate with the patient’s age and sex. Materials and Methods: Corneal button specimens received in the ocular pathology laboratory over a period of five years were reviewed. Histopathological features of Corneal Dystrophies were studied and subcategorised. Cliniopathological analysis was made. Results: Out of 660 corneal biopsies reviewed, 42 cases were of corneal dystrophy. The patients were between 2 and 71 years of age, with 14 males and 28 females. Macular dystrophy was the most common with 20 cases, followed by Congenital Hereditary Endothelial Dystrophy (CHED) and Fuch’s endothelial dystrophy (FECD), with 7 cases each. Epithelial basement membrane dystrophy, Reis Buckler Dystrophy (RBCD), Granular dystrophy were the other types. Conclusion: Histopathological sub categorisation of various types of Corneal Dystrophies not only helps in understanding the prevalence, but also in predicting the genetic link and prognosis of the disease category. Keywords: Cornea, CHED, Dystrophy, Fuch, Macular.

Demography of corneal dystrophies at a tertiary eye care centre in South India

To report the frequency of corneal dystrophies. All patients who presented to the out-patient department were examined for signs of corneal dystrophy from January 2017 to December 2019. All patients underwent a thorough evaluation for demographics, clinical presentation, history of consanguinity, family medical history, and clinical outcome of keratoplasty (in those who required it) and a clinicopathologic correlation was attempted. Complete ophthalmological examination was conducted for all patients which included vision (distance &amp; near), slit lamp examination, retinoscopy, auto refractometer readings, dilated fundus examination, pentacam as well as anterior segment OCT. Photographic documentation was done for all dystrophy patients. During this time period we had 118 patients who were included in the study. History of consanguineous marriage was noted in 62% of the study population. History of a similar problem in siblings and other members was elicited in 27 (22.88%) and 15 (12.71%) patients, respectively. 23 patients required keratoplasty. The average follow-up of each keratoplasty case was 36±14 months. Among these cases, only 2 groups had graft failure, viz, CHED and macular dystrophy. The higher frequency of dystrophies could be due to higher consanguineous marriage, which indicates a need for counselling. Also, there is an increased need for thorough work-up before planning intraocular procedures.

Multimodal imaging in subclinical best vitelliform macular dystrophy

BackgroundTo analyse multimodal imaging alterations in the subclinical form of best vitelliform macular dystrophy (BVMD).MethodsThe study was designed as an observational, cross-sectional case series. Eleven eyes of 7 subclinical patients...