Comprehensive review of angioid streaks.

ABSTRACT: Angioid streaks are irregular breaks in the brittle Bruch's membrane and commonly present as pigmented linear lines radiating from the optic disc. They may be associated with systemic disease in up to 50% of the patients. Systemic diseases such as pseudoxanthoma elasticum, Paget's disease, and hemoglobinopathies are commonly associated with angioid streaks. However, they may be idiopathic in a small number of cases. Patients may be asymptomatic until complications such as choroidal neovascular membrane and subretinal hemorrhage involving the fovea develop. Due to the brittle nature of Bruch's membrane, even minor trauma could lead to subretinal hemorrhage in these eyes. Diagnosis is commonly made through clinical examination and investigations such as fundus autofluorescence and optical coherence tomography. Treatment consists of management of the choroidal neovascular membrane commonly through intravitreal antivascular endothelial growth factor injections. In this review, we provide an overview of angioid streaks right from their epidemiology to their management.

A standardized Boswellia serrata extract shows improvements in knee osteoarthritis within five days-a double-blind, randomized, three-arm, parallel-group, multi-center, placebo-controlled trial.

Background: Boswellin® Super is a standardized extract of Boswellia serrata Roxb gum resin, standardized to contain 30% 3-acetyl-11-keto-ß-boswellic acid along with other ß-boswellic acids (BSE). A randomized, double-blind, placebo-controlled clinical trial was conducted at two doses of BSE to understand its safety and efficacy in supporting joint health and improving mobility and symptoms of osteoarthritis (OA) of the knee. Methods: Based on the inclusion/exclusion criteria, 105 newly diagnosed participants with degenerative hypertrophy OA were recruited and randomized into Placebo, BSE-150 mg or BSE-300 mg (n = 35 in each group) to receive either 150 mg or 300 mg BSE or a placebo tablet twice a day for 90 days. All the participants were evaluated for pain and physical function using the standard tools including the Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne Functional Index (LFI), EuroQol- 5 Dimension (EQ-5D) quality of life, 6-min walk test at day 0, days 5, 30, 60 and 90 of treatment. Additionally, the circulating levels of inflammatory biomarkers, tumor necrosis factor-α (TNFα), high-sensitive C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were evaluated. Safety was evaluated by blood biochemical, hematological analysis, urinary analyses and by monitoring adverse events throughout the study. Results: Ninety-eight subjects completed the study. Improvements in pain scores were observed as early as 5 days after the start of the supplement in the BSE-150 and BSE-300 groups. By 90 days, the VAS pain score reduced by 45.3% and 61.9%, WOMAC- total score improved by 68.5% and 73.6% in the BSE-150 and BSE-300 groups respectively. WOMAC pain (70.2%, 73.9%, WOMAC stiffness (65.6%,68.9%), WOMAC function (68.8%,74.2%), LFI severity (50%,53.3%), decreased and EQ5D (56.9%, 62.9%) and distance walked in 6 minutes (21.2%, 21.9%) improved in the BSE-150 and BSE-300 groups in 90 days. Further, the levels of TNFα, hs-CRP, and IL-6 were found to decrease in the serum in BSE-supplemented participants. No significant adverse events were recorded during the study. Conclusion: The study confirms that Boswellin® Super can be used as a safe and effective supplement to support joint health and mobility in the management of osteoarthritis. Clinical Trial Registration: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=NzU2Nzc=&Enc=&userName=CTRI, identifier CTRI/2022/11/047397.

Vitrectomy for cases of diabetic retinopathy.

ABSTRACT: Microvascular complications of diabetic retinopathy (DR) may require surgical intervention in the form of vitrectomy. Since its inception, diabetic vitrectomy has evolved with introduction of better instruments, newer techniques, and smaller port sizes. Common indications for diabetic vitrectomy include nonresolving vitreous hemorrhage, tractional retinal detachment, epiretinal membrane, progression of fibrovascular membranes despite laser therapy, recalcitrant diabetic macular edema, and neovascular glaucoma. Preoperative systemic stabilization is essential prior to planning surgery. Surgical techniques commonly used in diabetic vitrectomy are segmentation, delamination, and rarely en-bloc dissection. Modification in surgical techniques such as chandelier-assisted bimanual dissection and pharmacological adjuvants improve surgical outcomes in these patients. Prognosis in these patients could be improved with early intervention. Studies evaluating the outcome of vitrectomy in patients with early proliferative DR are required to understand the appropriate time of intervention in patients. Treatment aimed at arresting the progression of DR and gene therapy are avenues that need further evaluation. The following review will focus on covering the epidemiology of DR, indications of vitrectomy, preoperative considerations, surgical procedures of diabetic vitrectomy, methods of membrane dissection, pharmacological adjuvants to vitrectomy, outcomes of diabetic vitrectomy, and future directions of diabetic vitrectomy.

Topographic distribution of retinal neovascularization in proliferative diabetic retinopathy using ultra-wide field angiography.

Purpose: To analyze the topographic distribution of neovascularization (NV) and capillary nonperfusion (CNP) using ultra-wide field fluorescein angiography (UWFFA) in patients with proliferative diabetic retinopathy (PDR). Methods: This was a prospective, single-center, observational study in which all patients who presented between March 2019 and December 2020 and satisfied the inclusion criteria were recruited. In our study, patients with treatment-naïve PDR without any fibrovascular proliferation underwent UWFFA. The images were analyzed qualitatively for the topographic distribution of NV and the CNP area was quantified. The number of lesions picked by UWFFA was compared with 7 standard field (7SF) image using overlay of 7SF. The main outcome measure was characteristics of neovascularization, such as the number, location, and area of CNP, measured using UWFFA, which was considered with 95% confidence intervals (CI). Results: Two hundred and fifty-three eyes of 187 patients with a mean age of 56.03 ± 8 years were included. Mean neovascularization elsewhere (NVE) was 2.91 ± 3.43. Maximum NVEs were seen in the superotemporal (ST; 0.9 ± 1.13) quadrant, followed by the inferotemporal (IT; 0.7 ± 1.08), inferonasal (IN; 0.66 ± 1.02) and superonasal (SN; 0.66 ± 1.01) quadrants. Maximum CNP area was seen in the SN (13.75 ± 8.83 disc diameter square [DD2]) quadrant, followed by the IN (13.48 ± 8.59 DD2), IT (11.34 ± 8.37 DD2), and ST (11.3 ± 8.34 DD2) quadrants. Mean CNP area was maximum in patients with only neovascularization of disc (NVD; 64.99 ± 41.47 DD2), followed by both NVD and NVE (61.37 ± 35.61 DD2), and was minimum in patients with only NVE (36.44 ± 22.03 DD2). Eighty-one (32%) eyes out of 253 had NVE and 189 (75%) out of 253 had CNP area outside 7SF (overlay) of Early Treatment Diabetic Retinopathy Study (ETDRS). Conclusion: Diabetic NV lesions and CNP areas are distributed asymmetrically throughout the retina and are not restricted to the posterior pole. Compared to conventional 7SF imaging, UWFFA reveals significantly more retinal vascular pathology in patients with PDR.

Vitreous hemorrhage - Causes, diagnosis, and management.

Vitreous hemorrhage is associated with a myriad of conditions such as proliferative diabetic retinopathy, proliferative retinopathy following vascular occlusion and vasculitis, trauma, retinal breaks, and posterior vitreous detachment without retinal break. Multiple pathological mechanisms are associated with development of vitreous hemorrhage such as disruption of abnormal vessels, normal vessels, and extension of blood from an adjacent source. The diagnosis of vitreous hemorrhage requires a thorough history taking and clinical examination including investigations such as ultra-sonography, which help decide the appropriate time for intervention. The prognosis of vitreous hemorrhage depends on the underlying cause. Treatment options include observation, laser photo-coagulation, cryotherapy, intravitreal injections of anti-vascular endothelial growth factor, and surgery. Pars plana vitrectomy remains the cornerstone of management. Complications of vitreous hemorrhage include glaucoma (ghost cell glaucoma, hemosiderotic glaucoma), proliferative vitreoretinopathy, and hemosiderosis bulbi.

Comparison of two protocols of subthreshold micropulse yellow laser treatment for non-resolving central serous chorioretinopathy.

Purpose: To study the effect of subthreshold micropulse yellow laser treatment on central serous chorioretinopathy (CSC) and to compare two laser protocols. As per our knowledge, there are no studies comparing the two protocols of subthreshold laser. Methods: Twenty-three patients with non-resolving CSC of at least three months duration were treated with subthreshold laser (577 nm). Ten patients were treated with 5% duty cycle (group A) and 13 patients with 10% duty cycle (group B). At one month, best corrected visual acuity (BCVA), central macular thickness (CMT), subretinal fluid (SRF), choroidal thickness (CT) and choroidal vascularity index (CVI) were evaluated. Results: In group A, BCVA improved from 0.508 ± 504 to 0.174 ± 0.171 (P = 0.0058), CMT improved from 349.8 ± 168.9 micrometers (µm) to 183.3 ± 70.312 µm (P = 0.0093) and SRF reduced from 202.4 ± 158.024 to 43.8 ± 46.599 µm (P = 0.0069). In group B, BCVA improved from 0.437 ± 0.426 to 0.289 ± 0.470 (P = 0.0026), CMT improved from 280.846 ± 72.668 to 196.769 ± 72.62 µm (P = 0.0002) and SRF reduced from 110.385 ± 57.687 µm to 52.538 ± 52.111 µm (P = 0.0064). No significant difference was found in BCVA and CMT between the groups (P = 0.8716 and P = 0.8523, respectively). CSC completely resolved in 50% of cases in group A and in 69.2% of cases in group B. This difference was not statistically significant (0.423); however, the odds ratio of resolution was 2.25 times more with 10% duty cycle. No change was observed on fundus autofluorescence (FAF) following laser. Conclusion: Subthreshold micropulse laser can lead to resolution of SRF in 60.87% of cases (groups A and B combined). Ten per cent duty cycle had higher odds of resolution without causing any RPE damage.

A comprehensive review of intravitreal immunosuppressants and biologicals used in ophthalmology.

Systemic immunosuppressants and biologicals have been a valuable tool in the treatment of inflammatory diseases and malignancies. The safety profile of these drugs has been debatable, especially in localized systems, such as the eye. This has led to the search for fairly local approaches, such as intravitreal, subconjunctival, and topical route of administration. Immunosuppressants have been used as a second-line drug in patients intolerable to corticosteroids or those who develop multiple recurrences on weaning corticosteroids. Similarly, biologicals have also been used as the next line of therapy, when adequate control of inflammation could not be attained or immunosuppressants were contraindicated to patients. Intravitreal immunosuppressants, such as methotrexate and sirolimus, have been extensively studied in noninfectious posterior uveitis, whereas limited studies have established the efficacy of intravitreal biologicals, such as infliximab and adalimumab. Most of these drugs have shown good safety profile and tolerability in animal studies alone and have not been studied further in human subjects. However, most of the studies in literature are single-case reports or case series which limits the level of evidence. In this comprehensive review, we discuss the mechanism of action, pharmacodynamics, pharmacokinetics, indications, efficacy, and side effects of different intravitreal immunosuppressants and biologicals that have been studied in literature.

Role of optical coherence tomography-angiography in diabetes mellitus: Utility in diabetic retinopathy and a comparison with fluorescein angiography in vision threatening diabetic retinopathy.

PURPOSE: To determine the utility of optical coherence tomography-angiography (OCT-A) in diabetic retinopathy (DR) and comparison versus fluorescein angiography (FA) in vision-threatening diabetic retinopathy (VTDR). METHODS: In this cross-sectional observational study, 60 eyes with no DR (NDR), 60 eyes with non-proliferative diabetic retinopathy (NPDR), and 60 eyes with proliferative diabetic retinopathy (PDR) underwent OCT-A. FA was done in VTDR. OCT-A of the NDR eyes was analyzed by two independent retina specialists. Vessel density (VD) (mm/mm2), perfusion density (PD) (%), and foveal avascular zone (FAZ) (mm2) area was analyzed among the groups. Montage angiography with vitreoretinal interface (VRI) segmentation was done in PDR. A qualitative comparison was done between OCT-A and FA for features of DR. RESULTS: OCT-A detected 16.66% of the eyes with microaneurysm and 57.5% of the patients with capillary non-perfusion (CNP) areas in the NDR group. The inter-grader coefficient between the two observers was 0.820 for microaneurysm and 0.880 for CNP. The mean VD in NDR, NPDR, and PDR was 16.865, 13.983, and 11.643 mm/mm2. The mean PD in NDR, NPDR, and PDR was 30.595, 26.853, and 23.193%. The VD and PD values were statistically significant (P < 0.001). The mean FAZ area was not statistically significant (NPDR and PDR) (P > 0.05). The VRI showed elevated neovascularization in four eyes. OCT-A delineated microaneurysm and FAZ in 97/97 eyes who underwent FA. The FA failed to delineate FAZ in 2/37 NPDR eyes and 13/60 PDR eyes. The CNP areas (OCT-A) were detectable in all eyes. The FA demonstrated CNP areas in 17/37 and 36/60 eyes in NPDR and PDR, respectively. The FA could show peripheral CNP. CONCLUSION: The OCT-A helps in the early diagnosis of DR by providing vascular indices which are consistent with disease progression. OCT-A is non-invasive and ideal for follow-up. FA is a dynamic test with a larger field of view.