Characteristics of and treatment outcomes in rifampicin-intolerant patients.

BACKGROUND: Rifampicin (RIF) is considered the backbone of TB treatment, but adverse effects often limit its use. METHODS: This retrospective cohort study examined patients treated for TB disease at our institution, and compared those who received RIF to those who were intolerant to RIF. RESULTS: A total of 829 patients were included. Seventy-six patients (9%) were intolerant to RIF. Patients with RIF intolerance were significantly older (median age: 67 years, IQR 50-78 vs. 48 years, IQR 31-70; P < 0.0001), and were more likely to be female (57% vs. 41%; P = 0.01) and have concurrent diabetes mellitus (37.3% vs. 19%; P < 0.0001) compared to those who tolerated RIF. RIF intolerance was most commonly due to transaminitis (25%), cytopenia (14.5%), rash (17.1%) and gastro-intestinal intolerance (7.8%). Twenty patients were subsequently challenged with rifabutin, and this was successful in 70%. The mean treatment duration was significantly longer in patients who were intolerant to RIF (335 vs. 270 days; P < 0.001). There was no significant difference in treatment outcomes. CONCLUSION: RIF intolerance is more common in older patients, females, and those with concurrent diabetes mellitus. Patients who could not tolerate RIF had a longer duration of therapy, but no difference in treatment outcomes. When attempted, rifabutin was well tolerated in most patients with a previous RIF-related adverse event.

CONTEXTE: La rifampicine (RIF) est généralement considérée comme le pilier du traitement de la TB, cependant, ses effets indésirables limitent fréquemment son utilisation. MÉTHODES: Dans cette étude de cohorte rétrospective nous avons examiné les patients traités pour la TB dans notre institution et avons comparé ceux qui ont reçu la RIF à ceux qui n'ont pas pu la tolérer. RÉSULTATS: Au total, 829 patients ont été inclus. Soixante-seize patients (9%) étaient intolérants au RIF. Les patients intolérants au RIF étaient significativement plus âgés (âge médian : 67 ans, IQR 50­78 vs. 48 ans, IQR 31­70 ; P < 0,0001), et étaient plus susceptibles d'être des femmes (57% vs. 41% ; P = 0,01) et d'avoir un diabète sucré concomitant (37,3% vs. 19% ; P < 0,0001) par rapport à ceux qui toléraient le RIF. L'intolérance au RIF était principalement due à une transaminite (25%), une cytopénie (14,5%), une éruption cutanée (17,1%) et une intolérance gastro-intestinale (7,8%). Vingt patients ont ensuite été soumis à un test de provocation à la rifabutine, avec un taux de succès de 70%. La durée moyenne du traitement était significativement plus longue chez les patients intolérants au RIF (335 vs. 270 jours ; P < 0.001). Aucune différence significative n'a été observée dans les résultats du traitement. CONCLUSION: L'intolérance au RIF est plus courante chez les patients plus âgés, les femmes et les patients atteints de diabète sucré. Les patients qui n'ont pas pu tolérer le RIF ont suivi un traitement plus long, mais cela n'a pas entrainé de différence dans les résultats du traitement. Lorsqu'elle a été tentée, la rifabutine a été bien tolérée par la plupart des patients ayant déjà présenté un effet indésirable lié au RIF.

Effect of sustained-release long-acting intravitreal dexamethasone implant in patients of non-proliferative diabetic retinopathy undergoing phacoemulsification: A randomized controlled trial.

PURPOSE: Cataract and diabetes, both being a major health care problem, an intervention evaluated for the combination of the two attains paramount importance. The purpose of the study was to determine the role of intraoperative intravitreal dexamethasone implant in patients with diabetic retinopathy with/without macula edema undergoing phacoemulsification. METHODS: The study was a two-arm, single-center, randomized, assessor-blinded trial of 151 patients with type-2 diabetes mellitus and cataract. It had two groups: dexamethasone group (DEX) versus standard of care (SOC) group, i.e. phacoemulsification and intraocular lens (IOL) implantation without injection of dexamethasone drug delivery system (DDS). The number of rescue interventions required, central macular thickness by optical coherence tomography (OCT), Early Treatment Diabetic Retinopathy Study (ETDRS) score, laser flare meter (LFM) values, intraocular pressure (IOP), and grade of diabetic retinopathy (DR) were recorded until three months follow up. Macular thickness and number of rescue medications between the treatment groups were the co-primary outcomes. RESULTS: A statistically significant interaction was present between treatment and time on OCT score (P < 0.001). The requirement of rescue interventions in the dexamethasone DDS group [40.2% (33/82)] was lesser as compared to the SOC group [49.3% (34/69)] at the end of 12 weeks [odds ratio (OR), 0.70 (0.36-1.33)] follow up although not statistically significant (P = 0.343). A statistically significant interaction was present between treatment and time on LFM score (P = 0.003). No statistically significant interaction was present between the treatment and time on visual acuity score (P = 0.08) and IOP score (P = 0.375). CONCLUSION: Dexamethasone implant may have potential as a valuable therapy for patients undergoing cataract surgery with DR with/without macular edema with effects lasting for at least three months.

Screening for obstructive sleep apnea in a diabetic retinopathy clinic in a tertiary care center.

PURPOSE: : To screen for obstructive sleep apnea (OSA) in patients presenting to diabetic retinopathy (DR) clinic and to correlate its presence with the severity of DR. METHODS: : A prospective, cross-sectional study of diabetes mellitus patients in retina clinic of a tertiary care referral center, North India (January 2019-March 2020). All were subjected to STOP-Bang Questionnaire and Epworth Sleepiness Scale (ESS) score. Patients at high OSA risk (STOP-Bang score ≥5 and ESS score ≥10) were referred to Department of Otorhinolaryngology (sleep clinic) for polysomnography. Based on Apnea Hypopnea Index (AHI), OSA was graded as mild (AHI = 5-14/h), moderate (AHI = 15-30/h), and severe (AHI >30/h). Statistical analysis was done using three models of outcome measures: (1) "No DR" versus "any DR," (2) "Less severe DR" versus "More severe DR," and (3) "No diabetic macular edema (DME)" versus "DME." RESULTS: : Of 362 patients screened, 18 (4.97%) had OSA (11 mild, 5 moderate, and 2 severe). Though OSA did not show a significant association with various outcome measures, patients with moderate-severe OSA had higher odds in developing "any DR" (OR = 7.408; 95% CI = 0.533-102.898), "more severe DR" (OR = 1.961; 95% CI = 0.153-25.215), and "DME" (OR = 2.263; 95% CI = 0.357-14.355), on multiple logistic regression. CONCLUSION: : Ours is the first screening study of OSA in DR patients in India, the diabetes capital of the world. We detected OSA in 4.97% of patients in a DR clinic, with an increased risk of "any DR," "more severe DR," and "DME" in the presence of moderate-severe OSA.

Five-year demographic profile of retinopathy of prematurity at a tertiary care institute in North India.

Purpose: The purpose of this study is to study the demographic profile and pattern of retinopathy of prematurity (ROP) at a tertiary care institute in India. Methods: An ambispective study from January 2013 to December 2017. Infants with birth weights (BWs) <1750 g and gestational ages <34 weeks were screened for ROP. Demographic details and ROP severity were recorded. Results: Data of 2595 of the 3697 infants screened were analyzed. The number of infants screened and treated for ROP increased from 190 and 29, respectively (2013), to 818 and 132, respectively (2017). The overall incidence of "any ROP" was 32.3%, and severe ROP was 17.7%. Though 39.5% of all infants were outborns (not born in the study center), severe ROP was present in 69.7% of these compared to 18.8% among inborns. Outborns with ROP had a higher mean BW (1308 g) compared to inborns (1202 g) (P < 0.01). ROP Stage 1 was seen in 12%, Stage 2 in 34%, Stage 3 in 13%, Stage 4 in 6%, Stage 5 in 14%, and aggressive posterior ROP (APROP) in 20%. APROP was seen in 16% of infants in 2013, 10% in 2014, 15% in 2015, 22% in 2016, and 28% in 2017. Infants with Stage 4B/Stage5 (15.6% of all ROP) were presented at a mean age of 7.5 months and all had no/delayed screening. Conclusion: Incidence of any ROP was 32.3% and was more common in outborns than inborns. The proportion of infants with APROP showed a rising trend over the years. Nearly 15.6% of infants were presented with stage4B/5 ROP due to delayed/absent screening.

Enzymatic vitreolysis using reengineered Vibrio mimicus-derived collagenase.

Purpose: Collagen is a key player contributing to vitreoelasticity and vitreoretinal adhesions. Molecular reorganization causes spontaneous weakening of these adhesions with age, resulting in the separation of the posterior hyaloid membrane (PHM) from the retina in what is called complete posterior vitreous detachment (PVD). Incomplete separation of the posterior hyaloid or tight adherence or both can lead to retinal detachment, vitreomacular traction syndrome, or epiretinal membrane formation, which requires surgical intervention. Pharmacological vitrectomy has the potential of avoiding surgical vitrectomy; it is also useful as an adjunct during retinal surgery to induce PVD. Previously studied enzymatic reagents, such as collagenase derived from Clostridium histolyticum, are nonspecific and potentially toxic. We studied a novel collagenase from Vibrio mimicus (VMC) which remains active (VMA), even after deletion of 51 C-terminal amino acids. To limit the activity of VMA to the vitreous cavity, a fusion construct (inhibitor of hyaluronic acid-VMA [iHA-VMA]) was made in which a 12-mer peptide (iHA, which binds to HA) was fused to the N-terminus of VMA. The construct was evaluated in the context of PVD. Methods: VMA and iHA-VMA were expressed in Escherichia coli, purified, and characterized with gelatin zymography, collagen degradation assay, fluorescamine-based assay, and cell-based assays. Two sets of experiments were performed in New Zealand albino rabbits. Group A (n = 10) received iHA-VMA, while group B (n = 5) received the equivalent dose of VMA. In both groups, saline was injected as a control in the contralateral eyes. Animals were monitored with indirect ophthalmoscopy, optical coherence tomography (OCT), and B-scan ultrasonography. Retinal toxicity was assessed with hematoxylin and eosin (H&E) staining of retinal tissue. Results: The activity of iHA-VMA and VMA was comparable and 65-fold lower than that of C. histolyticum collagenase Type IV. In the iHA-VMA group, all the rabbits (n = 10) developed PVD, with complete PVD seen in six animals. No statistically significant histomorphological changes were seen. In the VMA group, four of the five rabbits developed complete PVD; however, retinal morphological changes were seen in two animals. Conclusions: iHA-VMA displays targeted action confined to the vitreous and shows potential for safe pharmacologic vitreolysis.

Ocular Tuberculosis in Human Immunodeficiency Virus and Systemic Tuberculosis Co-infected Patients.

Purpose: To describe the prevalence and clinical findings of ocular tuberculosis (TB) in Human immunodeficiency virus (HIV) and systemic TB co-infected patients.Methods: In this prospective, observational, non-comparative case series, we included HIV and systemic TB co-infected patients, who underwent a detailed ophthalmic and systemic evaluation.Results: Of 85 patients, ocular tuberculosis was seen in eleven patients and their 16 eyes (12.9%). Without the benefit of eye exam, the diagnosis of disseminated TB was missed in 5/52 (9.6%) and 2/25 (8%) of patients clinically assumed to have pulmonary and Extrapulmonary TB, respectively.Conclusion: HIV patients with the disseminated TB have higher risk for ocular TB. As ocular symptoms are rare, still all of them need a detailed ocular examination to look for active ocular TB which will reclassify isolated pulmonary/extrapulmonary to disseminated TB warranting a detailed systemic examination.

Endogenous endophthalmitis due to Staphylococcus aureus in a lactating woman.

Endogenous endophthalmitis (EE) is a rare but fulminant intraocular infection that needs prompt recognition and management. Bacteria are the commonest causative organisms and they may colonize the eye secondary to hematogenous spread from a focus anywhere in the body. EE in the peripartum period is an infrequent occurrence with no cases reported to occur secondary to a peurperal mastitis. We report a case of EE due to Staphylococcus aureous in a lactating female and describe its clinical presentation and management.

Outcome of pars plana vitrectomy in patients with retinal detachments secondary to retinal vasculitis.

PURPOSE: Retinal detachments (RD) secondary to retinal vasculitis are highly complex. We report the clinical profile and outcome of vitrectomy in RDs secondary to retinal vasculitis in terms of intraoperative findings, final anatomical, and functional outcome. METHODS: In a retrospective review of 68 patients (6 with bilateral RD; 74 eyes) undergoing pars plana vitrectomy (PPV) between 2000 and 2015 for vasculitic RD, tractional RD was present in 50 (67.57%) eyes and combined RD in 24 (32.43%) eyes. RESULTS: The mean age was 31.54 ± 9.95 years (62 males, 6 females). Fibrovascular proliferations (FVPs) involved major vascular arcades (22.98%), optic disc (10.81%), both arcades and disc (20.27%), peripheral retina (32.43%), and arcades with peripheral retina (13.51%). A total of 14 (18.92%) eyes had retinal folds, of which 9 had macular drag. Of 24 eyes with combined RD, 3 (12.5%) eyes had macular hole, 15 (62.5%) eyes had the primary retinal break anterior to equator, and 6 (25%) eyes had the primary break posterior to equator. Twenty-one (28.38%) eyes had iatrogenic retinal breaks. Thirty-eight (51.35%) eyes required an internal tamponade [gas in 31 (81.57%) eyes and silicon oil in seven (18.42%) eyes]. A scleral buckle was additionally required in 26 (35.14%) eyes. Postoperative complications included vitreous hemorrhage (27.03%), re-RD (12.16%), and iris neovascularization (9.46%). The median follow-up was 18 months (range 6-122 months). Sixty-eight (91.9%) eyes achieved final anatomical success. Fifty-two (70.27%) eyes had ≥2 lines visual improvement. CONCLUSION: Vasculitic RDs are complicated by tractional/combined RDs, peripherally located FVPs, retinal folds and iatrogenic retinal breaks, and carry a moderate prognosis.

Author Correction: Induction of posterior vitreous detachment (PVD) by non-enzymatic reagents targeting vitreous collagen liquefaction as well as vitreoretinal adhesion.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Induction of posterior vitreous detachment (PVD) by non-enzymatic reagents targeting vitreous collagen liquefaction as well as vitreoretinal adhesion.

Induction of posterior vitreous detachment (PVD) by pharmacologic vitreolysis has been largely attempted through the use of enzymatic reagents. Ocriplasmin has been the only FDA-approved clinical reagent so far. Several adverse effects of ocriplasmin have emerged, however, and the search for alternative PVD-inducing reagents continues. Since i) collagen forms an important structural component of the vitreous, and ii) strong vitreo-retinal adhesions exist between the cortical vitreous and the internal limiting membrane (ILM) of the retina, an effective PVD-inducing reagent would require both, vitreous liquefaction, and concurrent dehiscence of vitreoretinal adhesion, without being toxic to retinal cells. We designed a combination of two reagents to achieve these two objectives; a triple helix-destabilizing collagen binding domain (CBD), and a fusion of RGD (integrin-binding) tripeptide with CBD (RCBD) to facilitate separation of posterior cortical vitreous from retinal surface. Based on in vitro, ex-vivo, and in vivo experiments, we show that a combination of CBD and RCBD displays potential for safe pharmacologic vitreolysis. Our findings assume significance in light of the fact that synthetic RGD-containing peptides have already been used for inhibition of tumor cell invasion. Proteins such as variants of collagen binding domains could have extended therapeutic uses in the future.

Ultra-Widefield Fundus Autofluorescence in Cytomegalovirus Retinitis.

Purpose: To study the role of ultra-wide field (UWF) fundus autofluorescence (FAF) in the management of CMV (cytomegalovirus) retinitis.Material and methods: In this prospective, observational, non-randomized study, we followed up patients with active CMV retinitis on UWF fundus photograph (FP) and UWF-FAF.Results: A total of 16 patients (24 eyes) were studied. There were 13 males and mean age of patients was 37 (range 9-56) years. On UWF FP, out of 24 eyes, 13 (54.2%) had granular lesions, 3 (12.5%) had necrotizing pattern, 1 (4.1%) had a frosted branch angiitis (FBA), and 7 (29.2%) had a mixed pattern. UWF-FAF showed better delineation of borders of lesions in 7 eyes (29.1%), larger area of involvement in 8 eyes (33.3%), picked up 7 of 9 (77.77%) eyes of recurrence and helped differentiate cotton wool spots from retinitis lesion in one eye.Conclusion: UWF-FAF is useful in the management of CMV retinitis.

Prospective validation of a novel visual analogue uroflowmetry score (VAUS) in 1000 men with lower urinary tract symptoms (LUTS).

INTRODUCTION AND AIMS: Family physicians are limited by lack of tools to monitor benign prostate hyperplasia. VAUS provides a cost-effective, easily administered non-invasive tool. Our primary aim was to validate VAUS correlation with uroflowmetry measured maximal flow rate (Qmax), voided volume and International Prostate Symptom Scores (IPSS) symptom scores. Secondary aim was to study how the VAUS fared at predicting poor flow (Qmax < 10 ml/s) compared to age, voided volume and IPSS. Tertiary aim was to predict the best VAUS as a cutoff for poor flow. METHODS: After IRB approval, 1000 patients were prospectively recruited. They had VAUS, uroflowmetry and IPSS performed. VAUS is a novel five-point visual analogue scoring of urine flow, with one being the weakest and five the strongest. Data were analysed using SPSS where spearman's correlation coefficient and logistic regression analysis were performed looking for significance. Receiver operating curves (ROC) curves were used to identify best VAUS cutoff. RESULTS: 1000 patients were studied with mean age of 68.99 (50-95). VAUS showed good correlation with Qmaxp < 0.001, voided volume p = 0.006 and IPSS p <0.001. On multivariate analysis both VAUS and voided volume predicted poor flow significantly with p value of<0.001 and p =0.001, respectively. On ROC analysis VAUS of 2.5 was identified as best value for predicting poor flow with p value <0.001. CONCLUSION: VAUS is a validated tool for monitoring of lower urinary tract symptoms in our patients showing significant correlation with uroflowmetry, voided volume and IPSS.

Spectrum of Newly Diagnosed Cytomegalovirus Retinitis in a Developing Country in the HAART Era.

Purpose: To characterize the presenting features of cytomegalovirus (CMV) retinitis in HIV-positive patients in a developing country in the HAART era.Methods: Retrospective chart review of all patients with CMV retinitis seen at a tertiary-care referral center between January 2006 to June 2017. Demographic and clinical data were collected to study the presenting features and risk factors for blindness.Results: Fifty-five patients with treatment-naïve CMV retinitis were enrolled; 75% were males. CD4 counts were below 50 cells/µL in 51.1%. Bilateral presentation was seen in 61.5%. Half (50.6%) of the eyes were blind at first examination. Zone 1 involvement was present in 46% of the eyes. Retinal area involvement > 25% was the only factor associated significantly with higher incidence of blindness (p = 0.016).Conclusions: There was extensive and bilateral presentation of CMV retinitis due to delayed presentation. Screening for CMV retinitis, irrespective of CD4 counts, may help in developing nations.

Optical Coherence Tomography Angiography in Amblyopia.

BACKGROUND AND OBJECTIVE: The posterior segment of the eye has been investigated in the pathogenesis of amblyopia, but no abnormalities have yet been reported consistently. PATIENTS AND METHODS: In this prospective study, treatment-naïve amblyopes aged 6 years to 12 years with best-corrected visual acuity in the amblyopic eye between logMAR 0.3 and logMAR 0.7 and logMAR 0.1 or better in the contralateral eye were recruited. All patients underwent optical coherence tomography angiography (OCTA) imaging of the retina and choriocapillaris. RESULTS: The mean age of the 14 recruited patients was 10.26 years ± 1.31 years. The choriocapillaris vessel density was found to be attenuated in the amblyopic eye as compared to the fellow eye. There was a significant difference in the choriocapillaris vessel density between the amblyopic (39.61% ± 0.45%), and the fellow eye (44.10% ± 0.37%; P = .005). The choriocapillaris vessel density correlated positively with the visual acuity (r = 0.41; P = .03). CONCLUSION: The pathogenesis of amblyopia may involve the choriocapillaris, which is the primary source of blood supply for the photoreceptors. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e294-e299.].

Silicone band loop myopexy for myopic strabismus fixus.

Myopic strabismus fixus causes inability of the eye to elevate and abduct in the setting of a myopic superotemporally herniated globe. We report a novel surgical technique to manage an 18-year-old male with myopic strabismus fixus. Radiological imaging demonstrated a nasally deviated superior rectus (SR) and inferiorly displaced lateral rectus (LR). Silicone band assisted myopexy of SR and LR was done along with anchoring them to the sclera with a dacron suture. The patient had satisfactory alignment postoperatively and did not require any intervention over 1-year follow-up.