Copper, Lysyl Oxidase Activity, and Collagen in Aqueous Humour of Primary Glaucoma: An Association with Clinical Parameters.

INTRODUCTION: To measure copper (Cu), lysyl oxidase (LOX) activity, and collagen levels in aqueous humour (AH) of primary glaucoma patients and correlate with clinical parameters. METHODS: 120 patients with 40 each of primary open angle glaucoma (POAG), primary angle closure glaucoma (PACG), and cataract controls were recruited in this case-control study. AH samples were collected during the trabeculectomy and cataract surgeries. Cu levels were measured using an atomic absorption spectrophotometer. LOX unit activity was determined by Amplex Red assay and collagen concentration by Sirius red assay. RESULTS: Significantly higher levels of Cu expressed as median (IQR) µmol/L were observed in POAG (p = 0.008) and PACG (p = 0.005) compared to controls. The LOX activity was increased in POAG and PACG (p = 0.04) compared to controls represented as median (IQR) µmol/min. The collagen levels given as median (IQR) mg/ml showed an insignificant increase in POAG and PACG compared to controls (p = 0.78). The LOX unit activity was correlated with visual field index (VFI), which showed a significant increase with the progression of the diseases (p < 0.05), whereas Cu levels were negatively correlated with LOX activity in AH. Cu and LOX activity showed weak correlation with YAG peripheral iridotomy (YAGPI), duration of anti-glaucoma medications, and highest preoperative intraocular pressure. CONCLUSION: Elevated Cu and LOX activity was observed in both POAG and PACG groups compared to controls. LOX activity showed notable increase with VFI as the severity of the disease. Although Cu levels are increased in glaucoma, it's insufficient to significantly increase the activity of LOX.

Whole-genome sequencing unravels novel genetic determinants and regulatory pathways associated with triamcinolone acetonide-induced ocular hypertension.

Glucocorticosteroids commonly used to treat certain ocular inflammatory conditions cause an unwarranted elevation in intraocular pressure (IOP) leading to steroid-induced ocular hypertension (OHT). This study aims to identify novel genetic variants in the Indian population associated with steroid responsiveness, specifically to that of intravitreal Triamcinolone acetonide (TA) injections, which leads to OHT in 27% of the TA-treated Indian subjects. Genetic determinants and pathways regulating TA-OHT progression were investigated by applying whole-genome sequencing (WGS) on DNA extracted from 53 blood samples that included TA responders and non-responders. Sequencing analysis yielded 45 intronic and 49 exonic variants to be associated with TA-OHT, which are known to play a vital role in eye, heart, brain, and bone deformities. Of these, the most significant genetic variant associated with TA-OHT was further considered for molecular dynamics (MD) simulation studies. Variants in the CRPPA, PLOD1, ARHGAP1, TIMELESS and TNFSF4 genes were found to be directly implicating TA-OHT. Furthermore, these genes were enriched in pathways associated with cardiomyopathy, focal adhesion, extracellular matrix, and actin cytoskeleton reorganization. MD simulation studies revealed that the top significant variant (rs141625803) in the CRPPA gene possesses a high pathogenic and structurally destabilizing effect. Thus, novel genetic variants that could be significantly associated with the TA-OHT progression were identified in this study. Validation of these targets in a larger cohort of patients along with their functional analysis would inform on the disease, thereby adding to the existing knowledge on the pathophysiology of TA-OHT.

Association Between Gut Microbial Abundance and Sight-Threatening Diabetic Retinopathy.

Purpose: To study the association between gut microbial abundance and sight-threatening diabetic retinopathy among patients with a history of type 2 diabetes mellitus. Methods: An observational case-control study was performed using a sample population of diabetics referred to a tertiary eye institute. Sample subjects were identified as cases if they were diagnosed with sight-threatening diabetic retinopathy and controls if they were not but had at least a 10-year history of diabetes. Fecal swabs for all patients were collected for enumeration and identification of sequenced gut microbes. Statistical analyses were performed to associate the clinically relevant Bacteroidetes to Firmicutes relative abundance ratio (B/F ratio) with sight-threatening diabetic retinopathy and an optimal cutoff value for the ratio was identified using Youden's J statistics. Results: A sample size of 58 diabetic patients was selected (37 cases, 21 controls). No statistically significant difference in the relative abundance among the predominant phyla between the groups were found. In our univariate analysis, the B/F ratio was elevated in cases compared to controls (cases, 1.45; controls, 0.94; P = 0.049). However, this statistically significant difference was not seen in our multivariate regression model. Optimal cutoff value of 1.05 for the B/F ratio was identified, and significant clustering of cases above this value was noted in beta diversity plotting. Conclusions: No difference in gut microbial abundance for any particular phylum was noted between the control and diseased population. Increased gut microbial B/F ratio can be a potential biomarker for the development of sight-threatening diabetic retinopathy among type 2 diabetic patients.

Comparison of spectral domain optical coherence tomography parameters between disc suspects and "pre-perimetric" glaucomatous discs classified on disc photo.

Purpose: The aim of this study was to compare SD-OCT parameters between disc suspects and "pre-perimetric" glaucomatous discs classified on disc photos. Methods: Disc photos of suspicious discs with normal Humphrey visual fields (HVF) were graded as normal or pre-perimetric glaucomatous based on the consensus of three masked glaucoma specialists. RNFL and GCL-IPL maps of SD-OCT (Cirrus OCT) of these eyes were studied. Quantitative RNFL parameters were compared. Both groups were also compared with respect to parameters being classified as abnormal (at the 1% level), and the pattern of GCL-IPL and NFL maps were assessed qualitatively and classified as normal or pre-perimetric glaucomatous by a masked glaucoma specialist. Results: The average and inferior RNFL thicknesses were decreased in pre-perimetric glaucomatous eyes compared to normal eyes (p 0.01) The average, minimal, inferotemporal and inferior sector GCL-IPL thicknesses were decreased in pre-perimetric glaucomatous eyes (all P < 0.002) The highest AUC was for the inferior RNFL thickness (0.771) followed by average RNFL thickness (0.757) The sensitivity and specificity for any one abnormal RNFL parameter was 71.9% and 59.7%, for GCL-IPL parameters was 70% and 69.1% The positive (PLR) and negative likelihood ratios (NLR) were 1.78 and 0.47 for RNFL and 2.26 and 0.43 for GCL-IPL parameters. For the qualitative assessment of RNFL and GCL-IPL maps, the sensitivity, specificity, PLR and NLR were 75%, 77.2%, 3.29, and 0.32, respectively. Conclusion: Pre-perimetric disc suspects had greater OCT changes compared to normal disc suspects. Qualitative assessment of RNFL and GCL-IPL maps had the highest discriminatory ability.

Topical timolol for the treatment of conjunctival pyogenic granulomas: Outcomes and effect on intraocular pressure.

PURPOSE: To report the clinical outcomes of 0.5% timolol maleate eye drops for the treatment of conjunctival pyogenic granuloma (PG) and its effect on intraocular pressure (IOP). METHODS: In this retrospective study, consecutive patients with conjunctival pyogenic granuloma between January 2019 and September 2019 were prescribed 0.5% timolol maleate eye drops twice a day and followed up for 8 weeks. IOPs were measured before treatment, while on treatment and 6 weeks after treatment. RESULTS: A total of 12 patients with conjunctival PGs were treated with 0.5% timolol maleate eye drops. Patients ranged from 7 to 72 years with a mean age of 31.1 years. Eleven (11/12; 91.6%) patients had complete resolution of pyogenic granulomas after a mean duration of treatment of 4.4 weeks (range: 3-6 weeks). One patient had a persistent PG, which showed sub-optimal resolution at 6 weeks of treatment and was surgically excised. The mean IOP of the affected eye at presentation was 15.1 mm Hg (range: 10 to 20 mm Hg; SD: ±2.9 mm Hg). One week after initiating therapy, the mean IOP was 12.1 mm Hg (range: 8-16 mm Hg; SD: ±2.4 mm Hg). The mean reduction IOP compared to the baseline IOP was statistically significant (p = 0.02). No adverse events were noted in any of the patients. CONCLUSION: Topical timolol is effective in the treatment of conjunctival pyogenic granulomas with no major side effects. There is a significant reduction in IOP while on treatment which is reversible and returns to baseline following completion of therapy.

Phacoemulsification in eyes with long anterior zonules.

PURPOSE: To study the safety of phacoemulsification in eyes with long anterior zonules (LAZs). SETTING: Institute. DESIGN: Retrospective interventional case series. METHODS: All patients with clinically proven LAZs who had undergone phacoemulsification by a single surgeon from January 2014 to December 2018 were included. All cases of LAZs with cataract extraction by procedures other than phacoemulsification or combined with any other ocular surgery were excluded. Sixty-five eyes of 52 patients were analyzed. Phacoemulsification with capsulorhexis that involves sacrificing the LAZs was performed. The primary outcome measures were the incidence of capsulorhexis extension or the need to rescue intraoperatively and the rate of intraoperative complications. Secondary outcomes assessed were the percentage of eyes within ±0.5 diopters (D) and ±1 D of the target refraction. RESULTS: Sixty-five eyes (52 patients) were analyzed; the mean age of patients was 67.3 ± 7.4 years. The successful completion of an adequately sized capsulorhexis without extension or rescue was seen in 100% of cases. The incidence of intraoperative complications was 1.5% (posterior capsular rupture in 1 eye). The mean postoperative corrected distance visual acuity was 0.05 ± 0.1 (logarithm of the minimum angle of resolution) at a mean of 26.8 ± 7.6 days. The mean spherical equivalent was -0.15 ± 0.7 D. Eyes within ±0.5 D and ±1.00 D of the target refraction were 77% and 94%, respectively. CONCLUSIONS: Phacoemulsification in eyes with LAZs can be safely performed through an adequately sized capsulorhexis by sacrificing, ie, cutting or breaking, the anteriorly inserted zonules 360 degrees without significant intraoperative complications.

Construction and validation of logMAR visual acuity charts in seven Indian languages.

Purpose: The evaluation of visual impairment requires the measurement of visual acuity with a validated and standard logMAR visual acuity chart. We aimed to construct and validate new logMAR visual acuity chart in Indian languages (Hindi, Bengali, Telugu, Urdu, Kannada, Malayalam, and Assamese). Methods: The commonly used font in each language was chosen as the reference and designed to fit the 5 × 5 grid (Adobe Photoshop). Ten letters (easiest to difficult) around median legibility score calculated for each language based on the results of legibility experiment and differing by 10% were selected. The chart was constructed based on the standard recommendations. The repeatability of charts was tested and also compared with a standard English Early Treatment Diabetic Retinopathy Study (ETDRS) logMAR chart for validation. Results: A total of 14 rows (1.0 to -0.3 logMAR) with five letters in each line were designed with the range of row legibility between 4.7 and 5.3 for all the language charts. Each chart showed good repeatability, and a maximum difference of four letters was noted. The median difference in visual acuity was 0.16 logMAR for Urdu and Assamese chart compared to ETDRS English chart. Hindi and Malayalam chart had a median difference of 0.12 logMAR. When compared to the English chart a median difference of 0.14 logMAR was noted in Telugu, Kannada, and Bengali chart. Conclusion: The newly developed Indian language visual acuity charts are designed based on the standard recommendations and will help to assess visual impairment in people of these languages across the country.

Effect of Lignocaine Concentration on Human Fibroblasts Growth in Eyes Undergoing Trabeculectomy: An in vitro Study.

PURPOSE: To evaluate the effect of lignocaine on growth and apoptosis indication of primary human Tenon's capsule fibroblast (HTFs) in an in vitro model. PATIENTS AND METHODS: Tenon's capsule tissue obtained from patients undergoing trabeculectomy were grown in cell culture medium. The effect of different concentrations of lignocaine (0.5, 1.0, 1.5, and 2%) on the morphology and growth of the fibroblasts was studied using microscopy, cell viability, and proliferation assay, and apoptosis was detected using the FITC Annexin V Apoptosis Kit. RESULTS: Morphological changes similar to those of apoptotic cells, including cytoplasmic vacuolation, shrinkage, and rounding were visualized in the cells treated with concentrations greater than 1.0% (i.e., 1.5, 2.0%). Though proliferation inhibition was found with all four concentrations (0.5-2.0%), the viability of cells decreased from 1.0% lignocaine. CONCLUSION: 0.5% lignocaine prevents proliferation of fibroblasts without causing apoptosis in vitro.

Aripiprazole induced transient myopia: a case report and review of literature.

Aripiprazole is a drug belonging to the group of atypical antipsychotics. Ocular side effects of aripiprazole are rare. We report a case of transient myopia in a 33-year-old male who was being treated for schizophrenia with oral quetiapine and was recently supplemented with aripiprazole. One month after the addition of aripiprazole the patient reported sudden onset painless blurring of vision in both eyes. He was found to have myopia of-3.0 diopters in both eyes; his corrected visual acuity being 20/20. He was advised to discontinue aripiprazole. Ten days later on examination, the patient had an uncorrected visual acuity of 20/20 in both eyes. The stoppage of symptoms on stopping the drug indicates a strong correlation between the drug and the adverse effect. Ophthalmologists and psychiatrists must be aware of this reversible adverse drug reaction, so it may be treated promptly.

Peribulbar anesthesia for cataract surgery: effect of lidocaine warming and alkalinization on injection pain, motor and sensory nerve blockade.

AIM: To compare self-reported pain and efficacy of warmed, alkalinized, and warmed alkalinized lidocaine with plain 2% lidocaine at room temperature for peribulbar anesthesia in cataract surgery. MATERIALS AND METHODS: Through a prospective, single-blinded, randomized, controlled clinical trial 200 patients were divided into four groups. They received either lidocaine at operating room temperature 18 degrees C, control group (Group C), lidocaine warmed to 37 degrees C (Group W), lidocaine alkalinized to a pH of 7.09+/-0.10 (Group B) or lidocaine at 37 degrees C alkalinized to a pH of 6.94+/-0.05 (Group WB). All solutions contained Inj. Hyaluronidase 50 IU/ml. Pain was assessed using a 10-cm visual analog score scale. Time of onset of sensory and motor blockade and time to onset of postoperative pain were recorded by a blinded observer. RESULTS: Mean pain score was significantly lower in Group B and WB compared with Group C (P<0.001). Onset of analgesia was delayed in Group C compared with Group B (P=0.021) and WB (P<0.001). Mean time taken for the onset of complete akinesia and supplementation required for the block was significantly lower in Group B. Time of onset of pain after operation was significantly earlier in Group W compared with Group C (P=0.036). CONCLUSION: Alkalinized lidocaine with or without warming produced less pain than lidocaine injected at room temperature. Alkalinization enhances the effect of warming for sensory nerve blockade, but warming does not enhance alkalinization, in fact it reduces the efficacy of alkalinized solution for blocking the motor nerves in the eye.