Efficacy and Cost-Effectiveness of Anti-VEGF for Treating Diabetic Retinopathy in the Indian Population.

PURPOSE: In the present study, we aimed to evaluate the efficacy, safety, and cost-effectiveness of the anti-vascular endothelial growth factor (anti-VEGF), namely ranibizumab (RBZ) or bevacizumab (BVZ), after either focal or grid or scatter laser photocoagulation, for the treatment of diabetic macular edema (DME) in the Indian population. METHODS: Retrospective data were collected in the Regional Institute of Ophthalmology, Kolkata, India between January 2018 and June 2019. Seventy-seven eyes received 3 consecutive monthly intravitreal injections of RBZ (0.5 mg) and were followed by prompt laser photocoagulation (within 7-10 days after the third injection). Similarly, 51 eyes received 3 consecutive monthly intravitreal injections of BVZ (1.25 mg), an off-label drug, and were followed by prompt laser therapy. Safety assessments of the therapy, as well as surrogate markers of biochemical derangements related to diabetic retinopathy (DR), were also investigated at the end of 12 months. RESULTS: Seventy-seven subjects who were given a treatment of RBZ+laser therapy showed average 6.87±5.53 letters gain in their best-corrected visual acuity (BCVA) score, whereas the ones treated with off-label BVZ+ laser therapy demonstrated improvement in BCVA of an average 6.82±5.76 letters in "Early Treatment Diabetic Retinopathy Study" (ETDRS) chart. The study also highlights the cost-effectiveness of both RBZ+laser and BVZ+laser therapies for the treatment of DME in DR. The results demonstrated that a subject has to pay 20.951 times more cost (in INR) for RBZ+laser therapy compared to BVZ+laser therapy, to get an almost similar outcome. CONCLUSION: BVZ is found to be the more attractive option for treating DME in DR for its cost-friendliness over RBZ in terms of BCVA outcome, as well as the safety perspectives, at least for the economically backward population in developing countries, like India.

Pre-therapeutic Biomarkers for Ranibizumab Therapy among Type 2 Diabetic Patients with Diabetic Macular Edema.

SIGNIFICANCE: A differential outcome in randomized controlled trials of anti-vascular endothelial growth factor (anti-VEGF) therapy, including ranibizumab, for diabetic macular edema is a major dilemma for planning, optimizing, and managing clinical usage. The variable outcome of the therapeutics necessitates the importance of finding a predictive biomarker for anti-VEGF therapy to improve subject selection. PURPOSE: Our study correlates the baseline pro- and anti-VEGF isoforms and its three receptors (VEGFReceptor1, VEGFReceptor2, and VEGFReceptor3) for circulatory candidate protein molecules among diabetic patients with macular edema, with the clinical outcome of ranibizumab therapy. METHODS: This study included 86 individuals who were anti-VEGF naive at the time of ascertainment but have completed the standardized therapy regimen of the clinic. Plasma proteins for pro- and anti-VEGF isoforms and its three receptors were determined in replicate by an enzyme-linked immunosorbent assay. RESULTS: The study demonstrated that 56 (65.12%) individuals benefited from the therapy in terms of letter gain (Snellen chart). Baseline plasma soluble VEGF receptor 2 (sVEGFR-2) was significantly higher among responders (65.10 pg/mL; 95% confidence interval, 55.41 to 74.80 pg/mL) compared with nonresponders (46.38 pg/mL; 95% confidence interval, 38.69 to 54.07 pg/mL; PFDR = .03). Diffuse diabetic macular edema with proliferative diabetic retinopathy increases the risk of nonresponse to the therapy by 3.03-fold (PFDR = .04). CONCLUSIONS: The present study postulates that diffuse diabetic macular edema with proliferative diabetic retinopathy and baseline circulatory soluble VEGF receptor 2 may be potential candidates as therapy-stratifying markers for ranibizumab treatment among patients with diabetic macular edema.

Biochemical scenario behind initiation of diabetic retinopathy in type 2 diabetes mellitus.

Purpose: Despite the disease having similar glycemic status and duration microangiopathy in some patients develop within few years whereas it doesn't appear as a health complication in some diabetics for a considerable period. This study is undertaken to assess the hyperglycemia-induced biochemical background behind the development of diabetic retinopathy (DR) in type 2 diabetes mellitus (DM). Methods: Following proper diagnosis, 100 patients of type 2 DM of 10-12 years duration having no DR, and 42 patients of type 2 DM of the same duration and glycemic status as the second group, with mild retinopathy were recruited in the study. Lactic acid, glutamate, malondialdehyde (MDA), nitrate, advanced glycation end-products (AGEs), peripheral blood mononuclear cell reactive oxygen species (ROS), vascular endothelial growth factor (VEGF), and its receptor 2 (VEGFR2) in these two groups were produced in an assay following standard methodology. Results: Biochemical markers of anaerobic glycolysis, lipid peroxidation, AGEs, glutamate concentration, oxidative stress, and expression of VEGF and its VEGFR2 with significantly elevated markings were found in them who developed earliest stage of DR rather than them who had not. Conclusion: Hyperglycemia-induced anomalous glucose metabolism, lipid peroxidation, advanced glycation, glutamate toxicity, and oxidative stress create a background where apoptosis of retinal capillary endothelial cells invite increased expression of VEGF and VEGFR2, these being the crucial factors behind the development of diabetic microangiopathy.

p-Benzoquinone-induced aggregation and perturbation of structure and chaperone function of α-crystallin is a causative factor of cigarette smoke-related cataractogenesis.

Cigarette smoking is a significant risk factor for cataract. However, the mechanism by which cigarette smoke (CS) causes cataract remains poorly understood. We had earlier shown that in CS-exposed guinea pig, p-benzoquinone (p-BQ) derived from CS in the lungs is carried by the circulatory system to distant organs and induces various smoke-related pathogeneses. Here, we observed that CS exposure caused accumulation of the p-BQ-protein adduct in the eye lens of guinea pigs. We also observed accumulation of the p-BQ-protein adduct in resected lens from human smokers with cataract. No such accumulation was observed in the lens of never smokers. p-BQ is a strong arylating agent that forms Michael adducts with serum albumin and haemoglobin resulting in alterations of structure and function. A major protein in the mammalian eye lens is αA-crystallin, which is a potent molecular chaperone. αA-crystallin plays a key role in maintaining the integrity and transparency of the lens. SDS-PAGE indicated that p-BQ induced aggregation of αA-crystallin. Various biophysical techniques including UV-vis spectroscopy, fluorescence spectroscopy, FT-IR, bis-ANS titration suggested a perturbation of structure and chaperone function of αA-crystallin upon p-BQ modification. Our results indicate that p-BQ is a causative agent involved in the modification of αA-crystallin and pathogenesis of CS-induced cataract. Our findings would educate public about the impacts of smoking on eye health and help to discourage them from smoking. The study might also help scientists to develop new drugs for the intervention of CS-induced cataract at an early stage.

Quantitative Analysis of Segmented Fluorescein Angiography Images for the Follow-up of Choroidal Neovascular Membrane.

PURPOSE: The aim of this study was to evaluate choroidal neovascular (CNV) lesions with fluorescein angiography (FA) and to identify quantitative parameters and correlate these parameters to treatment outcomes. SUBJECTS AND METHODS: This institution based cross-sectional study evaluated 30 eyes with active sub-foveal predominantly classic CNV treated with bevacizumab. Pre- and post-injection segmented FA images were analyzed. Lesion area and CNV lesion were manually delineated. Outcome measure was the change 1-month after each injection in different intensity values (0-255 divided in eight regions A [lowest intensity] to H [highest intensity] on a linear scale) in lesion area, perimeter, greatest linear dimension (GLD), area, visual acuity (VA) and central macular thickness (CMT). RESULTS: At month 3, statistically significant changes from baseline occurred in VA, CMT, lesion area, GLD and perimeter (P < 0.05 all comparisons). Change in CMT from baseline to 3 months postinjection was correlated with change in VA (P = 0.009, r = 0.469) and intensity regions B (P = 0.001, r = -0.565), D (P = 0.001, r = 0.560), E (P = 0.035, r = 0.386). At month 3, change in intensity values 0-63 (A + B) was negatively correlated with CMT (P = 0.001, r = -0.575) and lesion area (P = 0.019, r = -0.427); change in intensity values 64-223 (C-G) was positively correlated with CMT (P = 0.000, r = 0.636) and lesion area (P = 0.002, r = 0.551). CONCLUSIONS: Decrease in area, GLD, perimeter and area with intensity ≥ 64 on segmented FA were associated with a favorable outcome of treatment. These parameters may be useful adjuncts to existing evaluation techniques during follow-up of CNV.

Limbal epithelial stem-microenvironmental alteration leads to pterygium development.

Maintenance of tissue homeostasis relies on the accurate regulation of tissue specific stem cell activity which is governed by the dynamic interaction between the positive and negative feedback modulating mechanism of stem cell microenvironmental niche. Alteration or deregulation of the "stem-microenvironmental networking" provokes disease development. Limbal epithelial stem cells (LESC) are the initiator hierarchy that maintains corneal integrity. Compartmentalization of LESC within the limbal vicinity provides an opportunity to understand the stem-microenvironmental relationship. The purpose of this study was to determine the microenvironmental alteration associated with LESCs fate in pterygium condition in comparison with healthy state. Clinical observations evaluated the ocular surface disorder with respect to corneal vascularization, tear film abnormality, and thickening of limbal area in pterygium patients. Structural alteration of limbal stem/progenitor cells and its neighboring niche components were observed using histology and scanning electron microscopy. Receptor overexpression of TGFß-R1, EGF-R1, and IL6-Rα and alteration of IL2-Rα expression pointed toward aberration of "stem-microenvironmental networking" in the limbal vicinity during disease development. Increased cell proliferation index along with TERT, Cyclin-D1, and PCNA over-expression in limbal part of pterygium epithelial cells indicated increased cellular proliferation and disturbed homeostatic equilibrium. We postulate that pterygium is associated with limbal microenvironmental anomaly where the resident epithelial cells became hyperproliferative.

A comparative study of two methods of optic disc evaluation in patients of glaucoma.

INTRODUCTION: Glaucoma is a progressive disorder and requires serial evaluation in order to monitor disease progression and optimize therapy. OBJECTIVE: The objective of this study was to determine the correlation between each of cup/disc (C/D) ratio and the disc damage likelihood scale (DDLS) with retinal nerve fiber layer (RNFL) and global indices in Humphrey field analyzer II (HFA II). DESIGN: Cross-sectional study. MATERIALS AND METHODS: A total of 50 patients diagnosed with primary open angle glaucoma were examined to grade DDLS score and C/D ratio. The average (avg) RNFL was obtained using the Fast RNFL protocol on optical coherence tomography (OCT) (4.0.2 Carl Zeiss). HFA II Swedish Interactive Threshold Algorithm Standard 24-2 visual fields were obtained within 1 month of clinical examination. The correlation of C/D ratio with avg RNFL thickness, Mean deviation and Pattern standard deviation was calculated by Pearson correlation coefficient (r). Similar coefficients were obtained for DDLS. RESULTS: The P value for the difference in the r between C/D ratio with RNFL (-0.628) and DDLS with RNFL (-0.8369) was significant (P < 0.01) when correlation of C/D, DDLS with RNFL was considered. CONCLUSION: The DDLS shows stronger correlation with structural changes in OCT than C/D ratio. The disc diameter and rim width increases the value of clinical optic disc examination.

Phenotypic alteration of limbal niche-associated limbal epithelial stem cell deficiency by ultraviolet-B exposure-induced phototoxicity in mice.

Good vision requires a healthy cornea, and a healthy cornea needs healthy stem cells. Limbal epithelial stem cells (LESCs) are a traditional source of corneal epithelial cells and are recruited for the continuous production of epithelium without seizing throughout an animal's life, which maintains corneal transparency. Like the maintenance of other adult somatic stem cells, the maintenance of LESCs depends on the specific microenvironmental niche in which they reside. The purpose of this study was to determine the microenvironmental damage associated with LESCs fate due to ultraviolet (UV)-B exposure in a mouse model. Structural alteration and deregulation of the stem cell and its neighboring niche components were observed by using clinical, morphological, explant culture study, and flowcytometric analysis, which demonstrated that the limbal microenvironment plays an important role in cornea-related disease development. In UV-exposed mice, overexpression of vascular endothelial growth factor receptor 2 indicated neovascularization, decreased CD38 expression signified the alteration of limbal epithelial superficial cells, and the loss of limbal stem cell marker p63 indicated limbal stem cell deficiency in the limbal vicinity. We concluded that LESC deficiency diseases (LESCDDs) are associated with pathophysiological changes in the LESC niche, with some inhibitory interception such as UV-B irradiation, which results in corneal defects.

Acute primary angle closure in a patient with high myopia: a case report.

Primary angle closure in a high myopic patient is rare. Here is presented a report of one such patient who presented with acute primary angle closure in one eye. Conservative management followed by laser iridotomy was effective in the treatment of this patient.

Visual impairment in urban school children of low-income families in Kolkata, India.

To evaluate pattern of visual impairment in school children from low-income families in Kolkata, India, an institutional cross-sectional study was conducted among 2570 children of 10 primary schools. Ocular examination including refraction was done and pattern of visual impairment and refractive error was studied. The age range was 6-14 years. Refractive error was seen in 14.7%. Only 4 children were already wearing correction. Myopia and hypermetropia was present in 307 (11.9%) and 65 (2.5%) children, respectively. Visual acuity of less than 6/12 in better eye was present in 109 (4.2%) and 5 (0.2%) children pre- and post-correction, respectively. Eighteen children had amblyopia. Although prevalence of refractive error in this group is less compared to school children of all income categories reported from other cities of India, it is more compared to school children of all income categories from the same city. Refractive error mostly remains uncorrected in this group.

Correlation of macular thickness and posterior hyaloid change following bevacizumab and triamcinolone in diffuse diabetic macular edema in middle-aged patients.

UNLABELLED: To compare changes in posterior vitreous detachment (PVD) following intravitreal injection of bevacizumab and triamcinolone in diffuse diabetic macular edema in middle-aged type 2 diabetes patients and to correlate this change with change in central macular thickness (CMT). DESIGN: cross sectional study. Fifteen consecutive patients treated by intravitreal bevacizumab (group A) and ten patients treated by intravitreal triamcinolone (group B). Institutional study carried out by retrospective analysis of patient registers including serial optical coherence tomography (OCT) images at baseline, and after 1 and 4 months. A central macular thickness (CMT) and vitreomacular relationship was noted on OCT. PVD was graded on a linear scale (0-4). Change in grade of PVD was correlated with change in CMT at each follow-up. At month 4, the decrease in mean CMT from baseline was 51.2 µ (P = 0.000) and 45 µ (P = 0.022) in group A and group B, respectively, with no significant difference between the two groups (P = 0.874). A change in grades of PVD from baseline to month 4 was significant in both group A (P = 0.001) and group B (P = 0.004) with no significant difference between the two groups (P = 0.906). A significant correlation between change in PVD and reduction of CMT was observed in group A (P = 0.011) but not in group B (P = 0.315). Both bevacizumab and triamcinolone caused a significant reduction in macular thickness and a significant change in grade of PVD. Change in PVD played an influential role in the reduction of macular thickness following bevacizumab.

A study on central corneal thickness and optic disc size in patients with primary open angle glaucoma.

The aim of the study was to evaluate a possible relationship between central corneal thickness (CCT) and optic disc area in patients with primary open angle glaucoma (POAG). Patients with POAG and age matched control group underwent routine ocular examination along with optic nerve head evaluation by Stratus optical coherence tomography (OCT) and CCT measurement by ultrasound pachymetry. Pearson's coefficient was calculated in both groups to find out correlation between these two parameters. In this series 90 eyes of 45 control subjects and 94 eyes of 47 POAG patients were studied. In the control group 40% were female, 60% male and among the POAG patients 34% female, 66% male. Mean CCT in control subjects was 566.98 micron (SD = 19.36, n = 90) and in POAG patients was 526.61 micron (SD = 29.93, n = 94). There was a significant difference in two groups (p = 0.0002). Disc area in control group had mean of 2.32mm(2) (SD = 0.305, n = 90) and in POAG group 2.982mm(2) (SD = 0.566, n = 94). Statistically significant difference was found among the two groups (p = 0.0). CCT was inversely correlated with optic disc size. In control subjects, r = -0.141, but it was not statistically significant (p = 0.092). In POAG group, r = -0.256 and the correlation was statistically significant (p = 0.0063). CCT was significantly less in POAG patients compared to control subjects. Mean disc area was significantly higher among the POAG group compared to control subjects. CCT was inversely correlated with disc area in both groups, but was statistically significant in POAG patients.

Hydatid cyst of orbit.

A 40-year-old woman presented with protrusion and diminution of vision of left eye for 3 months. CT scan of orbit revealed an intra-orbital cystic space occupying lesion. Exenteration of the left orbit was done and histopathological examination of the cystic mass proved it to be a case of hydatid cyst.

Ocular surface disorder in pterygium: role of conjunctival impression cytology.

OBJECTIVE: To study ocular surface abnormalities in patients with pterygium, conjunctival impression cytology was explored as a tool for the assessment of the cytological changes. MATERIALS AND METHODS: A comparative case control study was undertaken to evaluate the ocular surface disorders in pterygium. Fifty cases of pterygium and 50 age and sex-matched controls were analyzed for the presence of local tear film abnormalities as assessed by the tear film break up time and Schirmer test. The spectrum of changes in cytomorphology was studied in detail using conjunctival imprint cytology. RESULTS: Tear film break-up time and Schirmer's strip wetting were found to be significantly different in study and control groups. Studying the cytomorphology of the conjunctival imprint smears, reduced cellularity and squamous metaplasia of different grades was observed more frequently in patients compared to controls. On overall grading of cytological changes, statistically significant difference was noted between the study and control groups (P value 0.00172). CONCLUSION: From the present study we can suggest that aqueous tear film deficiency leading to ocular surface disorder brings about a change at the cytological level, and ocular surface disorders found in pterygium can be interpreted by conjunctival impression cytology.

An unusual case of penetrating ocular trauma with metallic spoon.

Ocular trauma is an important cause of vision loss. The agents incriminated in such injuries are diverse. We present a case of ocular trauma with a metallic spoon causing deep laceration of lid and temple region with sclerocorneal laceration. After assessment of the general condition and stabilization of the systemic parameters the operative procedure was undertaken on elective basis. Though the final visual outcome was not rewarding due to the severity of the injury, any potential hemostatic catastrophe was averted.

Prospective randomized comparative study of macular thickness following phacoemulsification and manual small incision cataract surgery.

PURPOSE: To compare macular thickness following uncomplicated phacoemulsification with foldable acrylic lens and manual small incision cataract surgery (MSICS) with non-foldable polymethyl methacrylate (PMMA) lens implantation. METHODS: Prospective study was carried out with one eye each of 224 patients with senile cataract randomized into two groups, phacoemulsification and MSICS, by simple 1:1 randomization. Following surgery by either of the two methods, macular thickness was measured by optical coherence tomography (OCT) on the 1st, 7th, 42nd and 180th postoperative day. Main outcome measure was postoperative macular thickness. RESULTS: On the first postoperative day, central subfield mean thickness (CSMT) in MSICS group was 192.8 +/- 17.9 microm and that in phacoemulsification group was 192.1 +/- 27.4 microm, with no significant difference (p = 0.12). On the 7th day, CSMT in MSICS group (198.9 +/- 21.4 microm) was significantly (p = 0.04) more than that in phacoemulsification group (193.1 +/- 19.3 microm). On the 42nd day, CSMT in MSICS group was 207.8 +/- 26.3 microm and that in phacoemulsification group was 198.3 +/- 23 microm, the difference being significant (p = 0.007). Clinically macular oedema was not diagnosed in any of the patients at any visit. The increase in macular thickness was sub-clinical and did not affect final visual outcome in any patient. CONCLUSION: In spite of the greater theoretical risk of increased postoperative inflammation following MSICS, there was no evidence of cystoid macular oedema, either clinically or on OCT. However, chance of sub-clinical increase in CSMT was more following MSICS compared to phacoemulsification.

Sca-1 expression pattern in the mouse limbal epithelium and its association with cell cycle.

Stem Cell Antigen-1 or Sca-1 is a cell surface receptor protein commonly used to detect adult murine haematopoietic stem cell population. Outside the haematopoietic system Sca-1 is similarly expressed in stem and progenitor cells in a wide variety of tissues and organs such as skeletal muscle, mammary gland, prostate, heart, liver and dermis. Thus Sca-1 has become a candidate marker in the search of tissue specific stem cells. The maintenance of a healthy corneal epithelium is achieved by a unique population of stem cell located in the limbal epithelial region. This limbal epithelium mainly contains limbal epithelial stem cells and its immediate progenitor early transient amplifying cells (e-TAC) which have self renewal capacity. As stem cells in other organs have been identified by their expression of Sca-1, in our study we wanted to determine whether this antigen could be present in the limbal epithelial region which contains stem cell population by using immunofluorescence through flow cytometric analysis of Sca-1 and its association with the cell cycle.

Central serous chorioretinopathy after dacryocystorhinostomy operation on the same side.

A 43-year-old man developed central serous choroidoretinopathy in his left eye following dacryocystorhinostomy operation on the same side. He was using xylometazoline nasal drops in his left nostril. Action of xylometazoline or the stress related to the operation or the effect of both factors played the role in the causation of this ocular condition. Omission of nasal drops or relief from stress resulted in full recovery of vision and complete resolution of symptoms within one month.