Beyond the phenotype: Exploring inherited retinal diseases with targeted next-generation sequencing in a Turkish cohort.

This research aims to compile recent clinical and genetic data from Turkish patients with inherited retinal disorders and evaluate the effectiveness of targeted Next-generation sequencing panels. The study included Turkish individuals with hereditary retinal diseases who visited the Medical Genetic Department of Erciyes University between 2019 and 2022. One proband per family was selected based on eligibility. We used Hereditary Disorder Solution (HDS) by Sophia Genetics and performed next-generation sequencing (NGS) with Illumina NextSeq-500. Bioinformatics analysis using Sophia DDM® SaaS algorithms and ACMG guidelines classified genomic changes. The study involved 354 probands. Disease-causing variants were found in 58.1% of patients, with ABCA4, USH2A, RDH12, and EYS being the most frequently implicated genes. Forty-eight novel variants were detected. This study enhances the knowledge of clinical diagnoses, symptom onset, inheritance patterns, and genetic details for Turkish individuals with hereditary retinal disease. It contributes to broader health strategies by enabling comparisons with other studies.

Inherited eye diseases in Turkey: Current approaches and future directions.

The aim of this review is to reveal Turkey's current status of medical practice in inherited eye diseases and the necessary steps to improve healthcare services and research activities in this area. Since consanguinity rate is high, disease burden is estimated to be high in Turkey. Universal health insurance system, easily accessible medical specialists, increasing genetic test, and counseling opportunities are the key advantages of Turkey's healthcare system. However, specialized clinics for inherited eye diseases, low-vision rehabilitation services, training of ophthalmologists about the recent developments in ocular genetics, and multidisciplinary translational research are the main headlines needed to be focused for better health services and successful research in Turkey.

Retinal vessel diameter obtained by optical coherence tomography is spared in Parkinson's disease.

PURPOSE: To define the alterations in retinal vessel diameter in Parkinson's disease (PD) by optical coherence tomography (OCT). METHODS: This is a case-control study including 41 eyes of 41 patients with diagnosis of PD and 35 eyes of 35 age- and sex-matched control subjects. All subjects underwent complete neurological and ophthalmological examinations before measurements. Retinal vessel diameters and peripapillary retinal nerve fiber layer (pRNFL) thicknesses were evaluated with spectral domain OCT (SD-OCT) with a circular scan centered at the optic disc. The diameters of the superior nasal and temporal arteries and veins, and inferior nasal and temporal arteries and veins were measured and then compared between the groups. Correlations with the duration of the disease, usage of levodopa, and pRNFL thicknesses between retinal vessel diameters were examined with Pearson and Spearman correlation analysis. RESULTS: Average pRNFL thickness is significantly decreased in PD compared to age- and sex-matched controls (p < 0.05). At all measurement points, retinal artery diameter measurements were decreased in the PD group compared to controls, but the differences did not reach statistical significance. Diameters of the retinal veins also did not show any significant difference in the PD and control groups. Superior temporal artery diameter was significantly decreased in patients using levodopa compared to nonusers (p = 0.022). There were no statistically significant correlations between pRNFL thicknesses or disease duration with retinal vessel diameters in PD group. CONCLUSIONS: Parkinson's disease does not seem to have an impact on the retinal vessel diameters obtained by SD-OCT.

Six-month results of suprachoroidal adipose tissue-derived mesenchymal stem cell implantation in patients with optic atrophy: a phase 1/2 study.

PURPOSE: This prospective clinical case series aimed to investigate the safety and efficacy of suprachoroidal adipose tissue-derived mesenchymal stem cell (ADMSC) implantation in patients with optic nerve diseases. METHODS: This prospective, single-center, phase 1/2 study enrolled 4 eyes of 4 patients with optic atrophy of various reasons who underwent suprachoroidal implantation of ADMSCs. The best-corrected visual acuity (BCVA) in the study was HM at 1 m. The worse eye of the patient was operated. Patients were evaluated on the first day, first week, first month, third and sixth months postoperatively. BCVA, anterior segment and fundus examination, color photography, optical coherence tomography (OCT) and visual field examination were carried out at each visit. Fundus fluorescein angiography and multifocal electroretinography (mfERG) recordings were performed at the end of the first, third and sixth months and anytime if necessary during the follow-up. RESULTS: All 4 patients completed the six-month follow-up. None of them had any systemic or ocular complications. All of the patients experienced visual acuity improvement, visual field improvement and improvement in the mfERG recordings. We found choroidal thickening in OCT of the 4 patients. CONCLUSION: Even though the sample size is small, the improvements were still encouraging. Stem cell treatment with suprachoroidal implantation of ADMSCs seems to be safe and effective in the treatment for optic nerve diseases that currently have no curative treatment options.

Ocular complications after cosmetic periocular diode laser application to the eyelids.

A 25-year-old woman underwent diode laser application on the both upper eyelids in the dermatology department of a private hospital to obtain a cosmetic healing of the reddish look on her eyelids without any protective lenses. The patient experienced severe uveitis, atonic pupils, raised intraocular pressure, and increased sensitivity to light in her eyes on the following day of the procedure. Topical steroids and pressure-lowering agents were able to treat the acute uveitis and glaucoma, unfortunately the patient suffered from irreversible atonic and atrophic pupils and photosensitivity. It is recommended that cosmetic laser application on the periocular area should be avoided, and if it is still to be performed, it should be applied cautiously and the patient should be informed of the potential ocular complications.

Evaluation of the effect of fluorescein angiography on retinal vessel diameter: an optical coherence tomography study.

PURPOSE: To evaluate the effect of fluorescein angiography on retinal vessel diameter with Optical Coherence Tomography (OCT). METHODS: In this cross-sectional study, a total of 81 eyes of 81 patients who were performed fluorescein angiography (FA) procedure were included. Retinal vessels were examined with the Spectral-domain OCT at baseline and immediately after FA procedure. A cube scan consisting of seven horizontal scans were placed at the inferior border of the disk to include the inferior temporal retinal vessels. Vessels diameters were measured at five measurement points (480-1440 µm inferiorly from the optic disk border). RESULTS: The mean age of the study subjects was 58.02 ± 14.1 years. At baseline, the mean diameter of the retinal artery was 120.16 ± 24.56 µm and of the vein 157.94 ± 32.34 µm at the measurement point of 480 µm, with a gradual decrease to 114.91 ± 25.59 and 152.17 ± 28.17 µm, respectively, at 1440 µm. After FA procedure, the mean diameter of the retinal artery was 122.85 ± 26.35 and of the vein 158.30 ± 32.21 µm at the measurement point of 480 µm, with a gradual decrease to 115.22 ± 22.91 and 151.94 ± 28.93 µm, respectively, at 1440 µm. There were no statistical differences for either of these comparisons at any of the points of both artery and vein measurements. CONCLUSION: There was not any clinically significant change in retinal artery diameter such as a dilatatory response after FA procedure in patients with hypertension, diabetes, and age-related macular degeneration (AMD).

IS THERE A ROLE OF ACTH IN INCREASED CHOROIDAL THICKNESS IN CUSHING SYNDROME?

PURPOSE: To evaluate choroidal thickness (CT) in patients with Cushing syndrome (CS) with enhanced depth imaging optical coherence tomography. METHODS: Twenty-eight patients with CS and 38 healthy volunteers were enrolled in this observational cross-sectional study. Patients with newly diagnosed CS who have been admitted to Erciyes University Department of Endocrinology in 3 years time interval were compared with age- and sex-matched healthy volunteers. Choroidal thickness was measured at the fovea and 2 points nasal and 2 points temporal to the fovea with 500-µm intervals each. RESULTS: Choroidal thickness measurements were higher in patients with CS than in the control group at all examination points; however, the difference was found to be significant at the center of the fovea (367.8 ± 94.4 µm vs. 329 ± 90.5 µm) and 1,000 µm temporal to the fovea. Choroidal thickness measurements were significantly higher in adrenocorticotrophic hormone (ACTH)-dependent CS group than in the control group at all measurement points (CT at fovea 388.2 ± 92.4 µm vs. 329.1 ± 90.5 µm). All CT measurements were found to be correlated with ACTH levels. CONCLUSION: Cushing syndrome is associated with increased CT. The ACTH-dependent CS may increase CT more than ACTH-independent CS. This effect may be directly related to ACTH itself or increased plasma cortisol levels or both.

Long-term prognosis of idiopathic nephrotic syndrome in children.

BACKGROUND: To investigate the demographic, clinical and laboratory data of the children with idiopathic nephrotic syndrome (INS), and to determine prognostic factors that affect the clinical outcome of the patients. METHODS: Medical charts of 372 patients diagnosed to have INS and followed up at least 5 years between January 1990 and December 2008 were evaluated, respectively. After initial demographic, clinical and laboratory findings of the patients were documented, therapeutic protocols, prognosis and prognostic factors were investigated. RESULTS: 299 of the patients (80.4%) were steroid responsive and 73 (19.6%) were not. Focal segmental glomerulosclerosis (FSGS) was observed in 57%, minimal change disease (MCD) in 20.6% and diffuse mesengial proliferation in 21.9% renal biopsy materials. Steroid sensitivity was higher in patients with MCD and under the age of five years. Resistance to steroids was higher in children with FSGS. Complete remission was achieved in 96% of patients who were sensitive to steroids and in 46.6% who were resistant. 15% of patients who were steroid resistant developed chronic kidney disease (CKD). CONCLUSION: Intercurrent infections and response to steroid therapy are the most important factors affecting the prognosis of the disease.

The relation between treatment and prognosis of childhood membranoproliferative glomerulonephritis.

BACKGROUND: The prognostic factors, the outcome and the most favorable treatment regimen are not entirely known for children with membranoproliferative glomerulonephritis (MPGN). MPGN is a rarely observed disease more prevalent in adolescents, so we aimed to review the clinical and histological properties, treatments and the outcome of our patients who were diagnosed as MPGN. METHODS: Fifty-one children - diagnosed with MPGN - were selected from biopsy records in Dr. Sami Ulus Maternity and Children's Hospital Pediatric Nephrology Department from January 1999 to January 2011. A retrospective analysis was made of 33 regularly followed children. RESULTS: Thirty-three patients were identified, 13 female and 20 male. Their age groups at presentation ranged from 4 to 15 years. The following duration was 26-144 months (mean 74). Following the initial treatment, 20 (60%) patients achieved complete remission. Six patients with nephrotic syndrome and one with non-nephrotic proteinuria showed partial remission. The condition of one patient with nephrotic syndrome was unchanged with the persisting symptoms. The one patient with nephrotic syndrome and four others with non-nephrotic proteinuria did not respond to initial treatment as their renal functions decreased gradually. CONCLUSION: We concluded that only degree of tubulointerstitial damage on the initial biopsy is determinative for prognosis of childhood MPGN. If the patient receives high doses of steroid therapy in the early stages, their treatment is more likely to be successful. The effect of immunosuppressive treatment on MPGN is not clear.

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.

ABCA4 variant screening in a Turkish cohort with Stargardt disease.

PURPOSE: This study aims to evaluate the ABCA4 variants in patients diagnosed with Stargardt disease. METHODS: This is a retrospective study designed to investigate variants in the ABCA4 in Stargardt disease and the clinical findings of the cases. Sex, age, age of onset of symptoms, best-corrected visual acuity, color fundus photography, optical coherence tomography, and visual field test of the patients were recorded. Genetic analyses were screened, and patients with at least two variants in the ABCA4 were included in this study. RESULTS: Twenty-seven patients diagnosed with Stargardt disease with the ABCA4 variants were included in this study. Twelve of them (44.4%) were female and fifteen (55.5%) were male. The mean age of the cases was 27.44 years (ranging from 8 to 56 years). Thirty different variants were detected in 54 ABCA4 alleles of 27 patients. The two most common pathogenic variants were c.5882 G>A p.(Gly1961Glu) and c.52C>T p.(Arg18Trp) in this cohort. Two novel variants were identified (c.3855_3856dup, c.1554 + 3_1554 + 4del) and the patient with the c.1554 + 3_1554 + 4del variant additionally had a different ABCA4 variant in trans. The other novel variant was homozygous. CONCLUSIONS: In this study, two novel variants were described in a Turkish cohort with Stargardt disease. The variant c.52C>T p.(Arg18Trp) was the most common disease-causing variant besides the c.5882 G>A p.(Gly1961Glu) which was identified frequently in the previous studies. A larger sample size is necessary for describing different pathogenic variants and understanding the phenotype-genotype correlations.

Identifying variants and their pathogenicity in inherited diseases is important for widening the disease-causing mutations and future treatment options.Two novel variants (c.3855_3856dup, c.5910_5912dup) were described in a cohort with Stargardt disease.The most common variants could be different in ethnic groups.The variant c.52C>T p.(Arg18Trp) was the most common variant besides the c.5882G>A p.(Gly1961Glu) which was frequently identified in the previous studies.Describing different pathogenic variants and clinical findings of the patients is important for understanding the phenotype-genotype correlations.

Changes in central corneal thickness, intraocular pressure, and oxidation/antioxidation parameters at high altitude.

BACKGROUND: The authors aimed at investigating ophthalmological changes at high altitude and correlating this with blood oxidation/antioxidation parameters. METHODS: There were 40 volunteers who participated in the study. Initial ophthalmological examinations were performed at 3543 ft (1080 m) and repeated on the following day after the participants climbed to an altitude of 9186 ft (2800 m) on Mt. Erciyes, Turkey. Venous blood samples were taken at both altitudes to evaluate total oxidative system (TOS) and antioxidative system (TAS) levels. RESULTS: IOP-right eyes at 3543 ft (1080 m) was 13.23 +/- 0.43 mmHg and significantly increased to 14.45 +/- 0.56 mmHg at 9186 ft (2800 m). LOP-left eyes at 3543 ft (1080 m) was 13.50 +/- 0.44 mmHg and increased to 14.13 +/- 0.54 mmHg at 9186 ft (2800 m) (P = n.s.). Central corneal thickness (CCT) of the right eyes was 540.98 +/- 4.34 microm at 3543 ft (1080 m) and significantly increased to 549.73 +/- 4.59 microm at 9186 ft (2800 m). CCT of the left eyes was 542.13 +/- 29.01 microm at 3543 ft (1080 m) and significantly increased to 547.23 +/- 4.59 microm at 9186 ft (2800 m). Spherical equivalent refraction of right or left eyes did not show any significant changes. TOS at 3543 ft (1080 m) was 5.33 +/- 0.76 micromol H2O2 equiv/L and significantly increased to 7.55 +/- 0.82 micromol H2O2 equiv/L at 9186 ft (2800 m). TAS at 3543 ft (1080 m) was 2.45 +/- 0.12 micromol H2O2 equiv/L and decreased to 2.22 +/- 0.08 micromol H2O2 equiv/L (P = n.s.) at 9186 ft (2800 m). There was a positive correlation between TAS and LOP at 9186 ft (2800 m). CONCLUSION: Increased CCT can be related to stromal edema caused by hypoxia's effect on corneal endothelial function. Although TOS increased at high altitude, TAS did not show any parallel increase. Since this was nonacclimatized climbing, the antioxidant system could not have reached sufficient levels to counterbalance the observed oxidant stress.

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.

Recombinant AhpC antigen from Mycobacterium bovis boosts BCG-primed immunity in mice.

Tuberculosis (TB) is still one of the most common infectious diseases around the world despite the widespread use of BCG (bacille Calmette-Guerin) strain of Mycobacterium bovis as a vaccine. This vaccine does not always protect people from TB, and, thus, new effective vaccines or vaccination strategies are being investigated. In this study, alkyl hydroperoxide reductase (AhpC) from M. bovis was evaluated as a new candidate vaccine antigen against TB in BALB/c mice model. The ahpC gene was amplified from M.bovis genome, cloned, and expressed in Escherichia coli. Vaccine antigen AhpC was formulated with Montanide ISA 61 VG, an oil-based emulsion adjuvant. Both IgG and IL-12 responses were observed in mice after administering the formulation both as a subunit vaccine alone and also as a booster vaccine for BCG immunization. However, a long-lasting response was observed when AhpC formulation was used as a booster (for BCG-primed immunization) as compared to being used as a subunit vaccine alone. In short, these findings suggested that AhpC has the potential to be used as a booster vaccine candidate for BCG-primed immunization.

Evaluation of Ring Amplitude and Factors Affecting Ring Amplitude in Multifocal Electroretinography in Diabetic Eyes.

PURPOSE: The aim of this paper was to evaluate the ring amplitudes in diabetic patients and to evaluate the effect of the risk factors for diabetic retinopathy on the ring amplitudes. We also aimed to investigate the success of ring amplitudes in classifying diabetic retinopathy. METHODS: The study included 32 eyes of 32 diabetic patients without retinopathy (DM), 34 eyes of 34 patients with mild non-proliferative diabetic retinopathy (NPDR) without macular edema, and 62 eyes of 62 age- and sex-matched controls (CG). All subjects were evaluated using mfERG. The relationship between age, diabetes duration, HbA1c and ring amplitudes and the effect of diabetes and hypertension on ring amplitudes were evaluated. Three-way ROC analysis was performed to evaluate the discrimination power of the ring amplitudes. RESULTS: In the comparison of the ring amplitudes, the amplitudes of the DM and NPDR groups were statistically significantly decreased compared to the CG (p < .05). A moderate to strong correlation was found between the duration of diabetes, HbA1c and ring amplitudes (p < .05). The effect of diabetes decreased towards the peripheral rings and hypertension did not affect ring amplitudes. Volume under the ROC surface of R1 = 0.65 had p < .05 and 95% CI [0.50-0.72], and the best cut-off point pair to differentiate the three classes was found to be c1 = 217.3, c2 = 151.2 in three-way ROC analysis. CONCLUSION: In conclusion, the effects of diabetes are unevenly distributed on the retina topographically. Diabetes affects the central rings more than peripheral rings in multifocal ERG. Both ring densities and ring ratios are effective ways to identify early changes in retinal function.

Respiratory-chain deficiency presenting as diffuse mesangial sclerosis with NPHS3 mutation.

Renal manifestations of mitochondrial cytopathies have been described, but nephrotic syndrome with respiratory-chain disorders have been described extremely rarely. We report a 9-month-old boy with a mitochondrial cytopathy preceded by a 2-month history of steroid-resistant nephrotic syndrome. Percutaneous renal biopsy revealed diffuse mesangial sclerosis, and mutational analysis was compatible with PLCE1 mutation. However, electron microscopic findings of renal tissue, sensorineural hearing loss, and other ocular and neurologic findings led us to suspect mitochondrial cytopathy. Muscle tissue analysis showed a deficiency of the respiratory chain complex IV. The clinical presentation of our patient is not typical for primary cytochrome oxidase (COX) deficiency but showed similarities with patients carrying AR mutations in COX10. This was the first case in the literature with both PLCE1 mutation and COX deficiency. We could not identify pathogenic mutations in the COX10 gene, suggesting that PLCE1 deficiency could be the cause of the secondary deficiency of COX. Another, more likely, possibility is that the mitochondriopathy phenotype is caused by another mutation homozygous by descent in a yet unidentified recessive gene.

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.

Correlation between optical coherence tomography angiography and multifocal electroretinogram findings in patients with diabetes mellitus.

BACKGROUND: Diabetic retinopathy is characterized by microvascular, neural and glial cell damage. Optical coherence tomography angiography (OCTA) can detect subclinical microvasculopathy while multifocal electroretinography (mfERG) can detect subclinical local retinal dysfunction before onset of clinically observable retinopathy. Here, we investigated the relationship between retinal dysfunction in multifocal electroretinography and vascular changes in optical coherence tomography angiography. METHODS: The study included 63 eyes of 63 diabetic patients without retinopathy (DM+DR-) and 68 eyes of 68 patients with non-proliferative diabetic retinopathy (NPDR). In addition, 64 eyes of 64 age and sex-matched subjects were included as the control group (CG). All subjects were evaluated using OCTA and mfERG. RESULTS: The vascular density in the superficial and deep capillary plexus was significantly decreased in the DM+DR-group and the NPDR group compared with the CG group (except for the superficial foveal area, NPDR group vs. CG group) (p < 0.05). The vascular density of the superficial and deep parafoveal region was significantly decreased in the NPDR group compared to the DM+DR-group (p < 0.05). In circles of 2-, 5- and 10°, the amplitudes of the N1 and P1 waves were statistically significantly decreased in both the DM+DR- group and the NPDR group compared with the CG (p < 0.05). When the NPDR group was compared with the DM+DR- group, there was a statistically significant decrease in the amplitude of the N1 and P1 waves in the circles of 2- and 5° (p < 0.05). According to the correlation analysis, the amplitude and implicit times of the N1 and P1 waves showed weak-to-moderate correlation with vascular density (p < 0.05). CONCLUSIONS: The decreased peaks of mfERG wave provides evidence regarding neurodegenerative effect of DM-associated hyperglycaemia. The decreased vascular density caused by hyperglycaemia was topographically associated with the retinal dysfunction and neurodegeneration.

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.