Intrafamilial Phenotype Variability in Two Male Siblings, With X-linked Juvenile Retinoschisis and Dorzolamide Treatment Effect in the Natural History of the Disease

To investigate how genotype is related to phenotype and document correlations of genotype-phenotype with response of topical administration of dorzolamide in siblings affected with X-linked juvenile retinoschisis (XLRS). We performed a retrospective study on two male siblings (four eyes) with XLRS, who were treated with topical installation of dorzolamide. Clinical diagnosis was supported with familial genetic analysis with bi-directional Sanger sequencing of RS1 pathogenic variant. Optical coherence tomography (OCT), fundus fluorescein angiography (FFA), ultrasound scan (U/S) and electroretinogram (ERG) were used in the evaluation. Central macular thickness (CMT) and best corrected visual acuity (BCVA) were recorded monthly for eighteen months. We performed genetic analysis in their family for mutations in the gene that encodes the protein retinoschisin, responsible for retinoschisis (RS1).  It was proved that phenotype variability might be related to the same pathogenic variant. While there was an improvement in BCVA and OCT central macular thickness in the patient with the mild form of disease, the visual acuity and the OCT scans of the patient with severe form of disease did not improve. Intrafamilial phenotypic variability between individuals sharing identical pathogenic variant was documented. Both our patients had a pathogenic variant in a hemizygous state at a genomic location in exon 6 of the RS1 gene; Frameshift mutation that is likely to cause protein truncation was identified which is suggested to result in greater clinical severity. Consequently, it was found that response to dorzolamide is correlated to phenotypic severity

Intrafamilial Phenotype Variability in Two Male Siblings, With X-linked Juvenile Retinoschisis and Dorzolamide Treatment Effect in the Natural History of the Disease

To investigate how genotype is related to phenotype and document correlations of genotype-phenotype with response of topical administration of dorzolamide in siblings affected with X-linked juvenile retinoschisis (XLRS). We performed a retrospective study on two male siblings (four eyes) with XLRS, who were treated with topical installation of dorzolamide. Clinical diagnosis was supported with familial genetic analysis with bi-directional Sanger sequencing of RS1 pathogenic variant. Optical coherence tomography (OCT), fundus fluorescein angiography (FFA), ultrasound scan (U/S) and electroretinogram (ERG) were used in the evaluation. Central macular thickness (CMT) and best corrected visual acuity (BCVA) were recorded monthly for eighteen months. We performed genetic analysis in their family for mutations in the gene that encodes the protein retinoschisin, responsible for retinoschisis (RS1).  It was proved that phenotype variability might be related to the same pathogenic variant. While there was an improvement in BCVA and OCT central macular thickness in the patient with the mild form of disease, the visual acuity and the OCT scans of the patient with severe form of disease did not improve. Intrafamilial phenotypic variability between individuals sharing identical pathogenic variant was documented. Both our patients had a pathogenic variant in a hemizygous state at a genomic location in exon 6 of the RS1 gene; Frameshift mutation that is likely to cause protein truncation was identified which is suggested to result in greater clinical severity. Consequently, it was found that response to dorzolamide is correlated to phenotypic severity

Electroretinogram changes before and after silicone oil removal in eyes with macula-off rhegmatogenous retinal detachment

Background: Pars plana vitrectomy (PPV) with silicone oil (SO) injection for rhegmatogenous retinal detachment (RRD) repair may adversely affect electroretinographic responses. This study was aimed at assessing retinal function using electrodiagnostic testing after successful PPV with SO tamponade in the eyes with macula-off RRD. Methods: In this interventional comparative study, eligible participants were recruited prospectively over 1 year. We included the eyes that underwent a single successful three-port PPV with SO tamponade for the primary repair of macula-off RRD. Full-field electroretinogram (ffERG) and multifocal electroretinogram (mfERG) were recorded 1 day before and 3 days after SO removal. The amplitude and implicit time of the a- and b-waves for ffERG and P1 and N1 waves for mfERG were evaluated. The unaffected fellow eyes of the patients were selected as controls. Results: We included the ten eyes of ten patients (seven men and three women) with a mean (standard deviation) age of 58.8 (6.2) years. The mean (SD) interval between the diagnoses of macula-off RRD and PPV was 11.7 (3.6) days. The mean (SD) duration of SO tamponade was 147.8 (34.9) days. Using ffERG, significantly lower a- and b-wave amplitudes were found in the eyes before and after SO removal or compared to the unaffected fellow eyes (all P < 0.05). Using the mfERG, treated eyes had significantly lower P1 amplitudes in the central R1+R2+R3 rings and in the R4 and-R5 peripheral rings of the macular area in the eyes before and after SO removal or compared to the unaffected fellow eyes (all P < 0.05). The wave implicit time in ffERG and mfERG did not differ significantly in the eyes before and after SO removal or compared to the unaffected fellow eyes (all P > 0.05). Conclusions: The electrical retinal response density in ERG waveforms increased following SO removal, indicating amelioration of the electrical activity of the retina and macula. These results indicate that the adverse effects of SO tamponade on electroretinography responses may be reversible with removal. In addition, ffERG and mfERG can be used to monitor retinal function in the eyes with macula-off RRD and SO tamponade. Further clinical trials are required to verify the preliminary findings of this study

Living with satisfactory vision and no comorbidity 28 years after bilateral retinoblastoma: a case report and mini literature review

Background: Retinoblastoma is the most common primary intraocular malignancy in children, although it is a rare neural retinal tumor. Improving the quality of life is the next goal after the primary medical goal of life preservation. The genotype-phenotype correlation may vary with the progression of retinoblastoma. Expressivity is determined by different RB1 gene mutations among individuals. Herein, we share our experience on the evaluation of the long-term progression of retinoblastoma, its treatment consequences, its impact on the quality of life, and how the underlying genotypes are related to the phenotypes. We provide a review of the relevant literature and present a case of a sporadic heritable bilateral retinoblastoma. Case Presentation: We report the outcomes of a 28-year follow-up of a female diagnosed with an infantile disease. The patient’s best eye, according to the tumor classification and genetic results, was treated conservatively whereas the worst eye was enucleated. On re-examinations, she had complications of the treatment she received. Therefore, another intervention was administered for several years. The patient’s pathogenic variant and RB1 gene mutational inactivation were predispositions to the recurrence of the tumor and non-ocular primary malignancy. Nevertheless, the disease had no progression. The patient is stable despite her type of retinoblastoma, which is the sporadic heritable bilateral form. Conclusions: Each phenotype of bilateral retinoblastoma varies in progression. The nature of the genetic mutation may determine its expressivity. It is of great significance to individualize every decision. In each case, the sequelae of the disease and treatment-induced complications may have an impact on the quality of the patient’s life

Role of intestinal microbiome in the pathogenesis of age-related macular degeneration

Background: The microbiome is strongly linked to many extra-intestinal disorders. Gut commensal microbiota, in particular, plays an active role in human immune and intestinal homeostasis. Complex interactions of the microbiota with host genetics and other underlying factors lead to intestinal dysbiosis, which is thought to be linked to ocular inflammatory diseases. Thus, the aim of this review is to analyze the role of intestinal microbiome in age-related macular degeneration (AMD). Methods: A thorough literature search was performed using PubMed/MEDLINE, limited to English language publications, from January 2004 to March 2020. An additional search was made employing Google Scholar to complete the collected data as per the above-mentioned time-line and language limitations. The main keywords used included age-related macular degeneration, microbiome, dysbiosis, autoimmunity, gut microbiota, epigenetics, immune-mediated inflammatory diseases, and gut-retina axis. Results: Recent studies have proposed the role of intestinal microbiota in the pathogenesis of AMD. Changes in the microbiome have been shown to trigger several ocular inflammatory processes. There is increasing evidence demonstrating that intestinal microbial imbalance may play an important role in the pathogenesis of AMD. Conclusions: This review summarizes how alterations in the intestinal microbiota can be associated with the pathogenesis of AMD and how new therapeutic modalities can be designed to target this microbiome to limit the severe nature of this disease. Future advances in microbiome research may unveil a new era in understanding and managing AMD

Strategy for the management of diabetic macular edema: the European Vitreo-Retinal Society macular edema study

Objective. To compare the efficacy of different therapies in the treatment of diabetic macular edema (DME). Design. Nonrandomized, multicenter clinical study. Participants. 86 retina specialists from 29 countries provided clinical information on 2,603 patients with macular edema including 870 patients with DME. Methods. Reported data included the type and number of treatment(s) performed, the pre-and posttreatment visual acuities, and other clinical findings.The results were analyzed by the French INSEE (National Institute of Statistics and Economic Studies). Main Outcome Measures. Mean change of visual acuity and mean number of treatments performed. Results.The change in visual acuity over time in response to each treatment was plotted in second order polynomial regression trend lines. Intravitreal triamcinolone monotherapy resulted in some improvement in vision. Treatmentwith threshold or subthreshold grid laser also resulted in minimal vision gain. Anti-VEGF therapy resulted in more significant visual improvement. Treatment with pars plana vitrectomy and internal limiting membrane (ILM) peeling alone resulted in an improvement in vision greater than that observed with anti-VEGF injection alone. In our DME study, treatment with vitrectomy and ILM peeling alone resulted in the better visual improvement compared to other therapies

Bilateral Macular Edema in a Patient Treated with Tamoxifen: A Case Report and Review of the Literature

We present a case of a 41-year-old female patient with progressive bilateral visual loss. On examination, her best corrected visual acuity (BCVA) in her right eye was 3/10 and her BCVA in her left eye was 2/10. Fundus and optical coherence tomography examination revealed severe bilateral macular edema. She had been diagnosed with breast cancer 6 years ago and was receiving tamoxifen at a dosage of 20 mg/day ever since. Tamoxifen therapy was discontinued, and the patient received 250 mg of acetazolamide three times a day for a period of 1 month. Both foveae regained their normal contour within 2 months, and her vision was restored to 10/10 BCVA 3 months later. To our knowledge, this is the first case reported where bilateral intraretinal macular edema is the only retinal manifestation in a patient on oral tamoxifen

Multifocal Central Serous Chorioretinopathy Associated with Steroids in a Patient with Myasthenia Gravis

We present a case of bilateral multifocal central serous chorioretinopathy in a 40-year-old male who suffered from myasthenia gravis and was receiving oral prednisolone. Due to the severity of the underlying disease, it was not possible to reduce the corticosteroid dose. After initial unsuccessful treatment with an intravitreal injection of ranibizumab, low-fluence photodynamic therapy was performed, followed by gradual tapering of the corticosteroids. Visual acuity improved significantly in both eyes. Different therapeutic approaches are discussed