Detailed Clinical, Ophthalmic, and Genetic Characterization of ADGRV1-Associated Usher Syndrome.

PURPOSE: To present the clinical characteristics, retinal features, natural history, and genetics of ADGRV1-Usher syndrome (USH). DESIGN: Multicenter international retrospective cohort study. METHODS: Clinical notes, hearing loss history, multimodal retinal imaging, and molecular diagnosis were reviewed. Thirty patients (28 families) with USH type 2 and disease-causing variants in ADGRV1 were identified. Visual function, retinal imaging, and genetics were evaluated and correlated, with retinal features also compared with those of the commonest cause of USH type 2, USH2A-USH. RESULTS: The mean age at the first visit was 38.6 ± 12.0 years (range: 19-74 years), and the mean follow-up time was 9.0 ± 7.7 years. Hearing loss was reported in the first decade of life by all patients, 3 (10%) described progressive loss, and 93% had moderate-severe impairment. Visual symptom onset was at 17.0 ± 7.7 years of age (range: 6-32 years), with 13 patients noticing problems before the age of 16. At baseline, 90% of patients had no or mild visual impairment. The most frequent retinal features were a hyperautofluorescent ring at the posterior pole (70%), perimacular patches of decreased autofluorescence (59%), and mild-moderate peripheral bone-spicule-like deposits (63%). Twenty-six (53%) variants were previously unreported, 19 families (68%) had double-null genotypes, and 9 were not-double-null. Longitudinal analysis showed significant differences between baseline and follow-up central macular thickness (-1.25 µm/y), outer nuclear layer thickness (-1.19 µm/y), and ellipsoid zone width (-40.9 µm/y). The rate of visual acuity decline was 0.02 LogMAR (1 letter)/y, and the rate of constriction of the hyperautofluorescent ring was 0.23 mm2/y. CONCLUSIONS: ADGRV1-USH is characterized by early-onset, usually non-progressive, mild-to-severe hearing loss and generally good central vision until late adulthood. Perimacular atrophic patches and relatively retained ellipsoid zone and central macular thickness in later adulthood are more often seen in ADGRV1-USH than in USH2A-USH.

Harboyan syndrome with biallelic SLC4A11 pathogenic variants misdiagnosed as congenital CMV infection.

Harboyan syndrome is a rare autosomal recessive disorder characterised by congenital hereditary endothelial dystrophy (CHED), with a later onset of sensorineural hearing loss, due to pathogenic variants in the SLC4A11 gene. Congenital cytomegalovirus (CMV) may also manifest with sensorineural hearing loss and visual impairment. We present a case of a 4-year-old girl, diagnosed at birth with a congenital CMV infection, but careful phenotyping and genetic testing permitted a more likely diagnosis of Harboyan syndrome.

Evaluation of ocular symptoms in COVID-19 subjects in inpatient and outpatient settings.

PURPOSE: Evaluation of subtle ocular involvement and clinically significant conjunctivitis symptoms in a group of patients with COVID-19 in outpatient and inpatient settings. METHOD: Overall, 1083 patients infected with SARS-CoV-2 were recruited as subjects. Patients were divided into inpatients (group 1, n = 371) and outpatients (group 2, n = 712). Demographical and general medical data included age, sex, and comorbidities. Patients whose diagnosis was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR) were called by phone, and their chronic ocular disease, previous ocular surgery, ocular medication, contact lens wear and ocular irritation symptoms were queried during the active disease period. RESULTS: The mean age of the patients was 44.2 ± 16.5 (19-97) years; 635 (58.6%) were male, and 448 (41.4%) were female. Comorbidity, chronic ocular disease, ophthalmic medication and previous ocular surgery rates were significantly higher in group 1 (p < 0.05), while contact lens wear was not significantly different between groups. The main complaints received from patients were sore eye or burning sensation, foreign body sensation, itching and red eye and were significantly higher in group 1. Clinically significant conjunctivitis symptoms, such as red eye, ocular discharge and eyelid edema, were observed in 28 patients (2.6%), with 14 (3.8%) patients in group 1 and 14 (2%) patients in group 2. CONCLUSION: Clinically significant conjunctivitis symptoms were detected in 28 subjects in the inpatient and outpatient groups. As systemic findings of COVID-19 intensify.

Comparison of success between external and endonasal dacryocystorhinostomy in primary acquired nasolacrimal duct obstruction in Turkish cohort.

OBJECTIVE: To evaluate the results and recurrence rates of external and endonasal dacryocystorhinostomy (DCR) surgery in patients with primary acquired nasolacrimal duct obstruction (PANDO) in Turkish Cohort. METHODS: Medical records were reviewed in all patients who underwent surgery for PANDO between January 2010 and September 2014 in a tertiary university hospital retrospectively. The patients were followed up on the first day, first month, third month and sixth month postoperatively. Lacrimal drainage system and recurrence rates were recorded. RESULTS: This study was conducted in 81 patients, 27 of whom were men (33.3%) and 54 were women (66.7%). The mean follow-up time was 30.13±16.42 months (range 6-62 months). The mean age was 50.51±12.47 years (range 16 to 77 years). External DCR was used in 44 (66.7%) of the cases and endonasal DCR was used in 37 (45.7%) of the cases. Surgical results of DCR were divided into three groups based on the integrity and openness of the lacrimal drainage pathway in all PANDO patients. Operation success rates of these data revealed that 45 (55.6%) cases were recorded as successful, 20 (24.7%) of the cases were accepted as partially successful and 16 (19.8%) of the cases were deemed as unsuccessful. Based on these data, surgical success rates were found in 38 (86.4%) patients in external DCR and 27 (73%) patients in endonasal DCR. Surgical failure rates were six (13.6%) in external DCR and 10 (27%) in endonasal DCR. There was no statistically significant difference between success rates and recurrences in both groups (p>0.05). CONCLUSION: Endoscopic DCR produced simple, minimally invasive and preferable results compared to external DCR in the Turkish population. Although the success of external DCR is higher and the recurrence is lower than endoscopic DCR, with the outcomes of this study, endoscopic DCR can be tried as the first choice to protect the patient from major surgery and anesthesia in PANDO.

Molecular and phenotypic investigation of a New Zealand cohort of childhood-onset retinal dystrophy.

Inherited retinal diseases are clinically heterogeneous and are associated with nearly 300 different genes. In this retrospective, observational study of a consecutive cohort of 159 patients (134 families) with childhood-onset (<16 years of age) retinal dystrophy, molecular investigations, and in-depth phenotyping were performed to determine key clinical and molecular characteristics. The most common ocular phenotype was rod-cone dystrophy in 40 patients. Leber Congenital Amaurosis, the most severe form of retinal dystrophy, was present in 10 patients, and early onset severe retinal dystrophy in 22 patients. Analysis has so far identified 131 pathogenic or likely pathogenic variants including 22 novel variants. Molecular diagnosis was achieved in 112 of 134 families (83.6%) by NGS gene panel investigation in 60 families, Sanger sequencing in 27 families, and Asper microarray in 25 families. An additional nine variants of uncertain significance were also found including three novel variants. Variants in 36 genes have been identified with the most common being ABCA4 retinopathy in 36 families. Five sporadic retinal dystrophy patients were found to have variants in dominant and X-linked genes (CRX, RHO, RP2, and RPGR) resulting in more accurate genetic counseling of inheritance for these families. Variants in syndromic associated genes including ALMS1, SDCCAG8, and PPT1 were identified in eight families enabling directed systemic care.

Pseudodominance in two families with KCNV2 related retinopathy.

PURPOSE: To describe the phenotypic and genotypic characteristics of two families with cone dystrophy with supernormal rod responses (CDSRR) presenting with a pseudodominant inheritance of disease. OBSERVATIONS: Three affected members from each family were ascertained. Family 1 of Egyptian ancestry showed consanguinity, and Family 2 was of Northern Iraqi ancestry. Both families showed pseudodominance in their pedigrees.Individuals presented with reduced visual acuity and nyctalopia. Macular disturbances were present in all, varying from a decreased foveal reflex to geographic atrophy. Electrophysiology showed reduced scotopic b-wave amplitudes and prolonged implicit times, and characteristic elevated b-wave amplitudes with high intensity flashes in all individuals.Genetic analysis of Family 1 identified a complete homozygous deletion of the KCNV2 gene, and in Family 2 a homozygous missense variation of c.562T > A: p.(Trp188Arg). CONCLUSIONS AND IMPORTANCE: To our knowledge this is the first report of pseudodominance of CDSRR, with a novel pathogenic KCNV2 variant present in the second family. Clinicians evaluating these individuals should consider autosomal recessive disease manifesting as pseudodominant inheritance. In such cases, electrophysiology remains essential for making a definitive diagnosis.

Intravitreal Bevacizumab for Treatment of Central Serous Chorioretinopathy.

PURPOSE: To compare the outcomes of treatment with intravitreal bevacizumab (IVB) versus observation in central serous chorioretinopathy (CSCR). METHODS: In a retrospective comparative study, records of 45 patients with CSCR were reviewed. Twenty-two patients received IVB (1.25 mg/0.05 ml) while 23 subjects were observed. All subjects underwent measurement of best corrected visual acuity (BCVA) and intraocular pressure (IOP), dilated fundus examination and optical coherence tomography (OCT) imaging at baseline and follow up visits. Outcome measures included central macular thickness (CMT) and BCVA in logarithm of minimum angle of resolution (logMAR) notations. RESULTS: Mean age was 44.1 ± 9.3 (range: 24 to 64) years and mean follow-up period was 10.4 ± 11.2 (range: 3 to 43; median: 6) months. All patients demonstrated resolution of neurosensory detachment and improvement in visual acuity. At final visit, there was no significant difference in mean CMT between the IVB and observation groups (275 vs 284 µm, P> 0.05). Mean baseline logMAR visual acuity was 0.38 ± 0.24 in the IVB group which improved to 0.24 ± 0.31 at final follow-up (P = 0.011); mean baseline logMAR visual acuity was 0.42 ± 0.28 in the observation group and improved to 0.12 ± 0.18 (P = 0.001). Visual improvement was more marked in the observation group (0.30 vs 0.14 logMAR, P< 0.05) and mean final visual acuity was also significantly better (P = 0.05). CONCLUSION: There was no significant difference between IVB injection and observation in terms of anatomical outcomes of treatment for CSCR. In terms of visual outcomes, observation was superior to IVB injection.