Sandeep Saxena

Nitric oxide and oxidative stress is associated with severity of diabetic retinopathy and retinal structural alterations

The aim of the study was to determine plasma nitric oxide (NO) and lipid peroxide (LPO) levels in diabetic retinopathy and its association with severity of disease.

Interleukin-1 and Tumor Necrosis Factor-Alpha: Novel Targets for Immunotherapy in Eales Disease

Background: Eales disease is an idiopathic obliterative vasculopathy that primarily affects the peripheral retina of young adults. The authors evaluated interleukin 1 beta (IL-1β), interleukin-6 (IL-6), Interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-α) in the serum of patients with Eales disease stages for the first time. Methods: The study group consisted of 45 consecutive patients of Eales disease [inflammatory stage (n = 15) and proliferative stage (n = 30)] and 28 healthy controls. Immunoassays for the quantification of the levels of four cytokines including IL-1β, IL-6, IL-10, and TNF-α in the serum samples were performed using ELISA kits. Results: IL-1β, IL-6, IL-10, and TNF-α levels were found to be increased significantly in the inflammatory stage of Eales disease as compared to controls (p < .001). IL-1β levels decreased significantly during the proliferative stage of the disease as compared to the inflammatory stage (p = .03). TNF-α levels increased significantly during the proliferative stage as compared to the inflammatory stage (p = .02). Conclusions: Raised levels of IL-1β and TNF-α were observed in the inflammatory stage and persisted in the proliferative stage of the disease. The IL-1 system and TNF-α represent novel target for immunotherapy for controlling inflammatory activity and/or the associated long-term sequelae related to angiogenesis in Eales disease.

Photoreceptor inner segment ellipsoid band integrity on spectral domain optical coherence tomography

Spectral domain optical coherence tomography cross-sectional imaging of the macula has conventionally been resolved into four bands. However, some doubts were raised regarding authentication of the existence of these bands. Recently, a number of studies have suggested that the second band appeared to originate from the inner segment ellipsoids of the foveal cone photoreceptors, and therefore the previously called inner segment-outer segment junction is now referred to as inner segment ellipsoidband. Photoreceptor dysfunction may be a significant predictor of visual acuity in a spectrum of surgical and medical retinal diseases. This review aims to provide an overview and summarizes the role of the photoreceptor inner segment ellipsoid band in the management and prognostication of various vitreoretinal diseases.

Tumor necrosis factor-α-mediated severity of idiopathic retinal periphlebitis in young adults (Eales’ disease): implication for anti-TNF-α therapy

Tumor necrosis factor-alpha (TNF-α) is a pleiotropic inflammatory cytokine. Tumor necrosis factor-alpha was evaluated in the serum samples of patients with idiopathic retinal periphlebitis in young adults (Eales’ disease). Retinal periphlebitis was graded according to a new grading system based on severity of inflammation (grade 1–4). Quantification of the TNF-α levels was carried out using ELISA kit in the serum samples of young adults with idiopathic retinal periphlebitis (n = 17) and healthy controls (n = 17) of similar age. Tumor necrosis factor-α level was found to be significantly raised in cases with retinal periphlebitis as compared with controls (p < 0.001). Higher levels of TNF-α were found to be associated with increased severity of retinal periphlebitis. Tumor necrosis factor-α represents a novel target for controlling inflammatory activity in idiopathic retinal periphlebitis. Higher levels of TNF-α, in association with the increased severity of retinal periphlebitis, have implications for early anti-TNF-α therapy.

Association of serum Nε-Carboxy methyl lysine with severity of diabetic retinopathy

PURPOSE To correlate serum levels of N-epsilon-carboxy methyl lysine (N(ε)-CML) with severity of retinopathy, in vivo macular edema and disruption of external limiting membrane (ELM) and photoreceptor ellipsoid zone in type 2 diabetes mellitus (DM). METHODS Consecutive cases of type 2 DM [diabetes mellitus with no retinopathy (No DR) (n=20); non- proliferative diabetic retinopathy (NPDR) with diabetic macular edema (n=20); proliferative diabetic retinopathy with diabetic macular edema (PDR) (n=20)] and healthy controls (n=20) between the ages of 40 and 65 years were included (power of study=93.8%). In vivo histology of retinal layers was assessed using spectral domain optical coherence tomography. Every study subject underwent macular thickness analysis using the macular cube 512×128 feature. Disruption of ELM and photoreceptor ellipsoid zone was graded: grade 0, no disruption of ELM and ellipsoid zone; grade 1, ELM disrupted and ellipsoid zone intact; grade 2, both ELM and ellipsoid zone disrupted. Data were statistically analyzed. RESULTS The mean levels of N(ε)-CML were 31.34±21.23 ng/ml, 73.88±35.01 ng/ml, 91.21±66.65 ng/ml, and 132.08±84.07 ng/ml in control, No DR, NPDR and PDR respectively. N(ε)-CML level was significantly different between the study groups (control, No DR, NPDR and PDR) (p<0.001). Mean logMAR visual acuity decreased with increased levels of N(ε)-CML (p<0.001). The association of N(Ɛ)CML with the grades of disruption was found to be statistically significant (F value=18.48, p<0.001). Univariate analysis was done with N(Ɛ)-CML as a dependent variable. The values of N(Ɛ)-CML were normalized (log10) and were subjected to univariate analysis with fasting blood glucose level, glycosylated hemoglobin, central subfield macular thickness and cube average thickness among the diseased groups (NPDR and PDR) that act as confounders. It was found that none of the variables had significant effect on N(Ɛ)-CML (fasting blood glucose p=0.12, HBA1c p=0.65, central subfield macular thickness p=0.13, cube average thickness p=0.19). N(Ɛ)-CML tends to be a significant and important predictor of grade of ELM and ellipsoid zone disruption in diabetic retinopathy. CONCLUSIONS Increased N(ε)-CML levels are associated with increased severity of diabetic retinopathy, macular edema and structural changes in macula that is ELM and ellipsoid zone disruption, which serves as a prognosticator of visual outcome.

Advanced glycation end products and diabetic retinopathy

Studies have established hyperglycemia as the most important factor in the progress of vascular complications. Formation of advanced glycation end products (AGEs) correlates with glycemic control. The AGE hypothesis proposes that hyperglycemia contributes to the pathogenesis of diabetic complications including retinopathy. However, their role in diabetic retinopathy remains largely unknown. This review discusses the chemistry of AGEs formation and their patho-biochemistry particularly in relation to diabetic retinopathy. AGEs exert deleterious effects by acting directly to induce cross-linking of long-lived proteins to promote vascular stiffness, altering vascular structure and function and interacting with receptor for AGE, to induce intracellular signaling leading to enhanced oxidative stress and elaboration of key proinflammatory and prosclerotic cytokines. Novel anti-AGE strategies are being developed hoping that in next few years, some of these promising therapies will be successfully evaluated in clinical context aiming to reduce the major economical and medical burden caused by diabetic retinopathy.

Three-dimensional spectral domain optical coherence tomography imaging of the retina in choroidal tuberculoma

Introduction To study retinal imaging in choroidal tuberculoma by three-dimensional spectral domain optical coherence tomography (SD-OCT) for the first time. Methods QuantiFERON-TB GOLD test, colour Doppler imaging, fluoroscein angiography and SD-OCT were performed in an 18-year-old immunocompetent female patient. Results Three-dimensional imaging over the choroidal lesion revealed marked retinal elevation. Subfoveal neurosensory detachment along with serous retinal detachment resulted from effusion of fluid from the underlying choroidal lesion. Granularity of the outer photoreceptor layer and proliferating retinal pigment epithelium cells indicated chronicity of the underlying choroidal lesion abutting the retina. Antitubercular therapy, after 2 weeks, resulted in a resolution of the subfoveal neurosensory detachment, reduction in the serous retinal detachment and a decrease in retinal elevation. Conclusions Three-dimensional SD-OCT allows a spatial visualisation and documentation of retinal elevation. It also allows a detailed visualisation of the secondary retinal pigment epithelial and intraretinal changes and is helpful in monitoring the response to medication.

Topical bevacizumab for corneal neovascularization after penetrating keratoplasty

Purpose To evaluate the efficacy of topical bevacizumab for corneal neovascularization in graft rejection. Methods A 55-year-old man presented with corneal neovascularization and graft rejection 6 months following penetrating keratoplasty (triple procedure) in the left eye. His best-corrected visual acuity (BCVA) was counting fingers at 1 meter. He was administered topical bevacizumab (4 mg/4 mL) in a dose of one drop twice a day for 15 days. No adjunct therapy was given during bevacizumab administration. Results After 1 month, his BCVA improved to 20/120. Corneal vascularization and stromal haze regressed. After 6 months, his BCVA improved to 20/60 with further regression in corneal vascularization and stromal haze. At 9-month follow-up, he maintained BCVA of 20/60. Conclusions Short-term topical bevacizumab therapy may potentially offer a safer and more effective alternative in treating graft rejection after penetrating keratoplasty. (Eur J Ophthalmol 2009; 19: 870–2)

Studies on the preparation and plasma spherodization of yttrium aluminosilicate glass microspheres for their potential application in liver brachytherapy

Plasma spheroidization exploits the high temperature and high enthalpy available in the thermal plasma jet to melt irregularly shaped powder particles and quench them to get dense spherical particles. Plasma spheroidization is a versatile process and can be applied to metals, ceramics, alloys and composites to obtain fine spherical powders. Radioactive microspheres incorporated with high energetic beta emitting radioisotopes have been reported to be useful in the palliative treatment of liver cancer. These powders are to be prepared in closer range of near spherical morphology in the size range 20-35 microns. Inactive glass samples were prepared by heating the pre-calculated amount of glass forming ingredients in a recrystallized alumina crucible. The glass was formed by keeping the glass forming ingredients at 1700°C for a period of three hours to form a homogeneous melt. After cooling, the glass was recovered from the crucible by crushing and was subsequently powdered mechanically with the help of mortar and pestle. This powder was used as the feed stock for plasma spheroidization using an indigenously developed 40 kW plasma spray system. Experiments were carried out at various operating parameters. The operating parameters were optimised to get spheroidised particles. The powder was sieved to get the required size range before irradiation.

Increased serum urea and creatinine levels correlate with decreased retinal nerve fibre layer thickness in diabetic retinopathy.

Abstract Correlation of increased levels of serum urea and creatinine with retinal nerve fibre layer (RNFL) thinning on spectral domain optical coherence tomography (SD-OCT) was studied in diabetic retinopathy (DR). Sixty consecutive cases and 20 healthy controls were included. Cases were divided into three groups: without DR, non-proliferative DR with macular oedema and proliferative DR with oedema. Serum urea and creatinine were measured using a standard protocol. Average (RNFL) was measured using SD-OCT. Increased severity of DR was associated with decrease in levels of serum urea and serum creatinine levels. RNFL thinning correlated positively with increase in serum urea and creatinine levels.