Evaluation of Full-Field Stimulus Threshold Test Results in Retinitis Pigmentosa: Relationship with Full-Field Electroretinography, Multifocal Electroretinography, Optical Coherence Tomography, and Visual Field.

Objectives: The full-field stimulus threshold (FST) test was developed to evaluate the efficacy and safety of treatments of hereditary retinal diseases. In this study we performed the FST test in patients with retinitis pigmentosa (RP) and compared the results with findings from other ophthalmological tests. Materials and Methods: The study included 51 intermediate and advanced RP patients and 21 normal subjects. All patients and controls underwent routine examination and ophthalmological tests including visual field, optical coherence tomography, full-field and multifocal electroretinography (mfERG), and FST tests. During FST testing, the perception thresholds of retina to the white, blue, and red FST were determined in decibels. Results: The mean age of the patients and the controls were 35.2 and 33.5 years, respectively. For all RP patients, no response was obtained on full-field ERG. All subjects were able to perform reliable FST tests. The mean values of visual acuity and central macular thickness were significantly lower and visual field mean deviation values were significantly higher in the RP group than the controls. When we evaluated the mfERG findings, the mean P1 wave amplitudes in all rings were significantly lower and the mean peak times were significantly longer in RP patients than controls. In comparisons of FST test results, the mean values for white, blue, red and the difference between blue-red thresholds were significantly lower in the RP group than the control group. Conclusion: The FST test is a fast and a reliable exam which can be done in subjects with poor visual acuity and reduced visual field. The results of this study confirm that the FST test can measure retinal sensitivity in severely affected RP subjects with flat flash ERG.

Frequency of RPE65 Gene Mutation in Patients with Hereditary Retinal Dystrophy.

Objectives: Hereditary retinal dystrophies are a rare group of diseases which are heterogeneous in genotype and phenotype and result in total blindness. One of the genetic defects that cause hereditary retinal dystrophy is mutation of the RPE65 gene. Genetic therapy studies in hereditary retinal dystrophies have increased in number recently, and important developments have been reported in these studies. Voretigene neparvovec-rzyl (Luxturna, Spark Therapeutics), a gene therapy drug for retinal dystrophy associated with RPE65 mutation, received Food and Drug Administration approval in 2017. This study aimed to investigate the frequency and clinical findings of patients with RPE65 gene defects, which may be amenable to genetic treatment. Materials and Methods: The data of patients diagnosed with hereditary retinal dystrophy who were followed up between 2017 and 2021 were retrospectively reviewed. Of these, 460 patients with genetic analysis results were included in the study. The clinical findings of patients with homozygous (biallelic) RPE65 mutation were screened. Results: RPE65 homozygous gene mutation was detected in only 11 of 460 cases (2.39%). Genetic results of the cases were presented in detail. The inheritance patterns of the cases were autosomal recessive. The demographic data and clinical findings were defined. Conclusion: RPE65 gene mutation is a very rare disorder. Genetic screening has gained importance with the emergence of gene therapy alternatives. New treatment methods are promising in cases for which there was no chance of a cure to date.

Quantitative analysis of early retinal vascular changes in type 2 diabetic patients without clinical retinopathy by optical coherence tomography angiography.

PURPOSE: To investigate the quantitative differences in optical coherence tomography angiography (OCTA) data between type 2 diabetes patients without clinically detectable diabetic retinopathy (DR) and healthy subjects. METHODS: Thirty-nine patients with type 2 diabetes without DR and 41 age- and sex-matched healthy controls were recruited. The vessel density and foveal avascular zone (FAZ) area in the superficial capillary plexus and deep capillary plexus were measured using Nidek RS-3000 Advance® and compared between patient cohorts. Foveal vessel density (%) and FAZ (%) were also calculated. RESULTS: A significant decrease in vessel density has been observed in the deep capillary plexus of the patients compared to healthy individuals (5.58 ± 0.98 mm2 versus 6.15 ± 0.89 mm2, p < 0.001). However, there were no significant differences in other parameters between cohorts (p > 0.05 in all parameters). Despite the decrease of deep capillary plexus density in the macular region, there was no significant change observed in foveal vessel density (p:0.44). It has also been observed that the duration of diabetes mellitus correlates with vessel density decrease in deep capillary plexus (R:-0.52; p < 0.001). In both groups, all parameters in deep capillary plexus were significantly higher than superficial capillary plexus (p < 0.001 for all parameters). CONCLUSIONS: OCTA can identify quantitative changes in DCP before the manifestation of clinically apparent retinopathy. DCP-VD reduction may be an earlier finding than FAZ enlargement. Despite the reduction of VD, FVD could be preserved for a certain period of time in DM patients.

Umbilical cord-derived mesenchymal stem cell implantation in patients with optic atrophy.

BACKGROUND: Optic nerve cells can be irreversibly damaged by common various causes. Unfortunately optic nerve and retinal ganglion cells have no regenerative capacity and undergo apoptosis in case of damage. In this study, our aim is to investigate the safety and efficacy of suprachoroidal umbilical cord-derived MSCs (UC-MSCs) implantation in patients with optic atrophy. METHODS: This study enrolled 29 eyes of 23 patients with optic atrophy who were followed in the ophthalmology department of our hospital. BCVA, anterior segment, fundus examination, color photography, and optical coherence tomography (OCT) were carried out at each visit. Fundus fluorescein angiography and visual field examination were performed at the end of the first, third, sixth months, and 1 year follow-up. RESULTS: After suprachoroidal UC-MSCs implantation there were statistically significant improvements in BCVA and VF results during 12 months follow-up (p < 0.05). When we evaluate the results of VF tests, the mean deviation (MD) value at baseline was -26.11 ± 8.36 (range -14.18 to -34.41). At the end of the first year it improved to -25.01 ± 8.73 (range -12.56 to -34.41) which was statistically significant (p < 0.05). When we evaluate the mean RNFL thickness measurements at baseline and at 12 month follow-up the results were 81.8 ± 24.9 µm and 76.6 ± 22.6 µm, respectively. There was not a significant difference between the mean values (p > 0.05). CONCLUSION: Stem cell treatment with suprachoroidal implantation of UCMSCs seems to be safe and effective in the treatment for optic nerve diseases that currently have no curative treatment options.

First Year Results of Suprachoroidal Adipose Tissue Derived Mesenchymal Stem Cell Implantation in Degenerative Macular Diseases.

BACKGROUND AND OBJECTIVES: This study shows the clinical data of 1-year follow-up of 8 patients with degenerative macular diseases who received suprachoroidal adipose tissue derived mesenchymal stem cell (ADMSC) implantation. METHODS AND RESULTS: This prospective, single-center, phase 1/2 study enrolled 8 eyes of 8 patients with degenerative macular diseases of various reasons who underwent suprachoroidal implantation of ADMSCs. All patients had severe visual field defects and severe visual loss. All patients had defective multifocal electroretinography (mf ERG). The worse eye of the patient was selected for the operation. Patients were evaluated on the first day, first month, sixth month and at 1 year postoperatively. Best corrected visual acuity (BCVA), anterior segment and fundus examination, color photography, optical coherence tomography (OCT) and visual field (VF) examination were carried out at each visit. Fundus fluorescein angiography (FFA) and mfERG recordings were performed at the end of the sixth months. All 8 patients completed the 1 year follow-up. None of them had any systemic or ocular complications. Seven of the patients experienced visual acuity improvement, visual field improvement and improvement in the mfERG recordings. We found choroidal thickening in OCT of the four treated eyes. CONCLUSIONS: Even though the sample size is small, stem cell treatment with suprachoroidal implantation of ADMSCs seems to be safe and the improvements were encouraging. To optimize the cell delivery technique and to evaluate the effects of this therapy on visual acuity and the quality of life of these patients, future studies with larger number of cases will be necessary.

Umbilical cord derived mesenchymal stem cell implantation in retinitis pigmentosa: a 6-month follow-up results of a phase 3 trial.

AIM: To investigate the efficacy and the safety of umbilical cord derived mesenchymal stem cell (UC-MSC) implantation in patients with retinitis pigmentosa (RP). METHODS: This prospective, single-center, phase 3 clinical study enrolled 124 eyes of 82 RP patients. The patients received 5 million UC-MSCs to the suprachoroidal area with a surgical procedure. Patients were evaluated on the 1st day, 1st, and 6th months postoperatively. Best corrected visual acuity (BCVA), anterior segment and fundus examinations, color photography, optical coherence tomography (OCT), and visual field (VF) tests were carried out at each visit. Fundus fluorescein angiography (FFA) and multifocal electroretinography (mfERG) recordings were performed at the end of the 6th month. Ocular and systemic adverse events of the surgical procedure were also noted. RESULTS: All of the 82 patients completed the 6-month follow-up period. None of them had any serious systemic or ocular complications. There were statistically significant improvements in BCVA and VF during the study (all P<0.05). The amplitudes of the P1 waves in the central areas showed significant improvements in mfERG recordings. There were also significant increases in implicit times of P1 waves in the central areas. CONCLUSION: Suprachoroidal administration of UC-MSCs has beneficial effect on BCVA, VF, and mfERG measurements during the 6-month follow-up period. Cell mediated therapy based on the secretion of growth factors (GFs) seems to be an effective and safe option for degenerative retinal diseases.