The Genetics of Ethambutol-Induced Optic Neuropathy: A Narrative Review.

Tuberculosis (TB) is a global health problem with the major brunt of disease occurring in developing countries. The cornerstone of treatment of TB is anti-tubercular therapy (ATT), which includes rifampicin, isoniazid, pyrazinamide and ethambutol. Because of emerging drug resistance, treatment failures, defaulters and increasing incidence of disseminated and extrapulmonary TB, the guidelines have been modified in some countries. Ethambutol is prescribed for longer times (in some cases >8 months) and hence the incidence of ethambutol-induced optic neuropathy (EtON) is expected to rise. The fundamental question which needs explanation is why only a small subset of patients on ethambutol are prone to develop loss of vision. This review focuses on available genetic studies which provide evidence that mitochondria are the likely substrates involved in the final pathway of reactive oxidative damage of the papillo-macular bundle. Genetic analysis of mitochondrial mutations encoding genes involved in oxidative phosphorylation pathways may help in isolating the subset of patients who are genetically susceptible. If the groups having high risk of developing EtON are recognised then prolonged duration of ethambutol treatment can be avoided in these susceptible individuals. A better understanding of the pathophysiology will also pave the way for the development of management strategies in this condition.

Long-Term Efficacy of Selective Laser Trabeculoplasty in Primary Angle-Closure Disease After Laser Peripheral Iridotomy.

PURPOSE: To evaluate the long-term efficacy of selective laser trabeculoplasty (SLT) in eyes with primary angle-closure (PAC) and primary angle-closure glaucoma (PACG) following a laser peripheral iridotomy (LPI). METHOD: In this prospective cross-sectional study, 45 eyes of 34 patients with PAC/PACG diagnosis, uncontrolled intraocular pressure (IOP), and visible pigmented trabecular-meshwork (TM) at least 180° on gonioscopy following a LPI were recruited. Following a detailed baseline ophthalmic evaluation, all eligible eyes underwent SLT, and the patients were examined on day1, at 1 week, 1-, 3-, and 6-months, and 1-, 2-, 3-, 4-, and 5-year subsequently. The main outcomes measured were IOP, number of IOP-lowering agents, and complications. RESULTS: The mean age of the cohort was 57.80 ± 6.44 years, the male-female ratio was 8:26, and 17 eyes were PACG, and 28 were PAC. The baseline IOP was 23.81 ± 1.78 mm Hg, and was significantly declined at all follow-ups (p < .0001). The cumulative probability of overall success was 91% and 84% at 2-, and 5-year, respectively. At 5-year SLT provided drug-freedom in 80% of PAC and 23% of PACG eyes. Six eyes had IOP spike at 1-week and two patients underwent repeat SLT after 1-year. No other complications, such as pain/discomfort, inflammation, an increase in peripheral anterior synechiae and cystoid-macular-edema, were noted. CONCLUSIONS: SLT appears a safe and cost-effective procedure in PAC/mild- moderate PACG eyes with uncontrolled IOP after laser iridotomy. The long-term effectiveness of SLT as adjuvant treatment was good, but need large sized randomized studies for more validation.

Intraoperative optical coherence tomography (I-OCT) assisted passage of the encircling element during retinal detachment surgery.

Objective: To describe the role of microscope integrated optical tomography (Mi-OCT) in passage of the encircling element during retinal detachment surgery. Materials and methods: Mi-OCT was switched on while passing scleral anchoring sutures to secure the encircling element. The depth of the suture tract was seen in real time while the needle was passed through the sclera. The amount of scleral intend achieved was assessed using Mi-OCT at the end of the surgery. Results: The depth of needle tract through the sclera and the amount of scleral indentation achieved while tying the sutures could be successfully analyzed using Mi-OCT. Conclusion: Mi-OCT can be used as an adjunct while training vitreoretinal fellows and trainees in surgical procedures like passage of scleral sutures for anchoring the encircling element.

Redrawing vitreoretinal surgical training program in the COVID-19 era: Experiences of a tertiary care institute in North India.

Purpose: The COVID-19 pandemic has brought medical and surgical training to a standstill across the medical sub-specialties. Closure of outpatient services and postponement of elective surgical procedures have dried up opportunities for training vitreoretinal trainees across the country. This "loss" has adversely impacted trainees' morale and mental health, leading to feelings of uncertainty and anxiety. Therefore, there is an urgent need to redraw the surgical training program. We aimed to describe a systematic stepwise approach to vitreoretinal surgical training. Methods: We introduced a three-pronged approach to vitreoretinal surgical training comprising learn from home, wet lab and simulator training, and hands-on transfer of surgical skills in the operating room in our institute. Results: Encouraging results were obtained as evaluated by feedback from the trainees about the usefulness of this three-pronged approach in developing surgical skills and building their confidence. Conclusion: The disruption caused by the COVID-19 global pandemic should be used as an opportunity to evolve and reformulate surgical training programs to produce competent vitreoretinal surgeons of the future.

Outcomes of 25-gauge pars plana vitrectomy for cytomegalovirus retinitis-related retinal detachment.

PURPOSE: The purpose of this study is to evaluate the anatomical and functional outcomes of 25-gauge (G) pars plana vitrectomy (PPV) in patients with cytomegalovirus retinitis (CMVR)-related rhegmatogenous retinal detachment (RRD). METHODS: Single-center retrospective consecutive case series of patients who underwent 25-G PPV for CMVR-related RRD repair with a minimum follow-up of 3 months. Complete anatomic success was defined as the complete attachment of retina including the periphery. Best-corrected visual acuity (BCVA) of ≥20/400 was defined as functional success. RESULTS: Sixteen eyes of 15 patients were included in the study. Eleven patients were human immunodeficiency virus positive, three patients had hematological malignancies, and one patient suffered from dyskeratosis congenita. The mean follow-up was 20.5 ± 17.4 months (range 3-60 months). Complete anatomical success was seen in 15 eyes (93.75%). One eye had a residual inferior detachment with attached macula. Silicone oil was used as tamponade in 15 eyes and C3F8 gas in one eye. The mean change in BCVA was statistically significant, preoperative LogMAR BCVA was 2.05 ± 0.94 while the final follow-up postoperative LogMAR BCVA was 1.03 ± 0.61 (P < 0.001). Thirteen eyes (81.25%) had final BCVA ≥20/400. CONCLUSION: Microincision vitrectomy surgery can achieve excellent retinal reattachment rates in post-CMVR RRDs without significant intraoperative and postoperative complications. The visual outcome varies depending on the status of the optic disc and macula. Majority of the patients maintained functional vision.

Outcomes of 25-gauge pars plana vitrectomy with encircling scleral band for acute retinal necrosis-related rhegmatogenous retinal detachment.

Purpose: The aim of this study was to evaluate the anatomic and functional outcomes of 25-gauge pars plana vitrectomy (25G PPV) with encircling scleral band (ESB) in patients with acute retinal necrosis (ARN)-related rhegmatogenous retinal detachment (RRD). Methods: Single-center retrospective interventional case series of patients who underwent 25G PPV with ESB for ARN-related RRD. Complete anatomic success was defined as the complete attachment of retina after primary PPV. Functional success was measured by the final best-corrected visual acuity (BCVA) ≥20/400. Intraoperative and postoperative complications were also noted. Results: 14 eyes of 13 patients were included in the study. Six patients (46.1%) were immunocompromised. The mean follow-up was 23.64 ± 9.95 (range 6-42) months. Silicone oil was used as tamponade in 13 eyes and C3F8gas in one eye. After the primary PPV, complete anatomical success was seen in all eyes (100%), however, one eye developed phthisis bulbi after silicone oil removal (SOR). Statistically significant improvement of BCVA was seen, from LogMAR 2.03 ± 0.29 preoperatively to LogMAR 1.57 ± 0.63 postoperatively (p-value 0.014). Six eyes (42.9%) had functional success. Nine eyes (64.3%) had improvement in vision while 4 eyes (28.6%) maintained preoperative vision. 10 eyes (71.4%) underwent cataract surgery, nine eyes (64.3%) underwent SOR while 2 eyes (14.3%) had epiretinal membrane (ERM) under oil during follow-up. Conclusion: 25G PPV combines the advantages of minimally invasive vitrectomy surgery while offering improved anatomic outcomes in patients with ARN-related RRD. The functional outcome varies depending on the status of the optic disc and macula.

Management of dislocated transscleral fixated intraocular lens with one-side broken polypropylene suture.

This video demonstrates the successful surgical technique for refixation of the same intraocular lens (IOL) by tying the same IOL to the sclera with the help of 9-0 polypropylene suture. A 62-year-old male patient presented with sudden loss of vision in the left eye. He had a history of undergoing transscleral fixation of intraocular lens (TSFIOL) using 10-0 polypropylene suture 13 years back for posttraumatic-dislocated nucleus. On examination, we noticed that he had IOL dislocation due to spontaneous breakage of suture of one of the haptic. The other haptic suture was intact. The long-term complication associated with TSFIOL procedure is breakage of the polypropylene suture leading to subluxation or dislocation of the IOL. We used closed-globe approach to successfully fixate the involved haptic of the same IOL. No intraoperative or postoperative complication was encountered in three such cases.

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.

Ocular mycobacteriosis-dual infection of M. tuberculosis complex with M. fortuitum and M. bovis.

BACKGROUND: We report unfavorable outcome in a patient with subretinal granuloma caused by dual infection of Mycobacterium tuberculosis complex with Mycobacterium fortuitum and Mycobacterium bovis in an immunosuppressed, non-HIV patient. We did a systematic review of literature on dual infection due to M. tuberculosis and M. fortuitum via MEDLINE and PUBMED and could not find any case reported of causing this kind of dual infection in the eye. RESULTS: A 38-year-old Indian male patient presented with decreased vision in the left eye for 3 months, diagnosed as tubercular choroidal granuloma with associated retinal angiomatosis proliferans (RAP) lesion. He also had multiple enlarged lymph nodes in the chest, and sternal pus sample was positive for acid-fast bacilli (AFB). M. tuberculosis complex was detected by gene expert. The patient was started on antitubercular treatment (ATT) whereby the lung lesions improved but the ocular lesion showed initial clinical improvement followed by worsening. Twenty-five-gauge diagnostic pars plana core vitreous surgery was done whereby sample demonstrated a large number of AFB on Ziehl-Neelsen stain and auramine-rhodamine stain. The vitreous sample showed growth on routinely inoculated mycobacteria growth indicator tube (MGIT) 960 tubes, and multiplex polymerase chain reaction (PCR), Gene Xpert MTB/ RIF assay (Cepheid, Sunnyvale, CA), and line probe assay (LPA) were positive for ocular tuberculosis. In view of nonresponse to conventional ATT, a suspicion of dual infection of M. tuberculosis complex with a nontubercular mycobacteria was kept and a subculture was made onto the solid Lowenstein-Jensen (LJ) medium from the positive MGIT 960 tubes. Two morphologically distinct types of colonies were obtained on LJ slopes. Subsequently, the two etiological agents were identified as M. fortuitum and M. bovis by PCR from the vitreous sample. CONCLUSIONS: Co-infection of M. tuberculosis complex with nontubercular mycobacterium (NTM) has never been reported from ocular tuberculosis before. In immunosuppressed individuals, who test positive for MTB, not responding to the standard ATT, one needs to have a high index of clinical suspicion to rule out associated NTM infection and initiate appropriate multidrug systemic antibiotic therapy early.

Bevacizumab for paradoxical worsening treatment adjunct in HIV patient with choroidal tuberculoma.

The use of anti-tubercular therapy (ATT) along with anti-retroviral therapy (ART) in human immunodeficiency virus-tuberculosis (HIV-TB) co-infected individuals could at times lead to paradoxical worsening due to an increase in the inflammatory activity due to immune reconstitution inflammatory syndrome (IRIS) in the eye. This is characterized by anterior and posterior segment inflammatory reactions which may occur in the form of serous retinal detachment. We describe a case where the use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agent led to resolution of the serous retinal detachment, which had failed to respond to other common modalities of treatment.An HIV-TB co-infected 18-year-old, male patient, who was started on ART and ATT developed IRIS in the form of worsening of serous retinal detachment around a pre-existent asymptomatic tuberculoma. The patient was initially treated with oral and topical steroids without a satisfactory response. Intravitreal bevacizumab was then tried for this patient. Serial fundus photos and optical coherence tomography (OCT) taken before and after treatment showed complete resolution of the serous retinal detachment with two doses of intravitreal bevacizumab.Intravitreal anti-VEGF agents may have a role in the reversal of serous retinal detachment, which occurs as a part of IRIS in HIV-tuberculosis co-infected individuals who have been started on anti-tubercular and anti-retroviral therapies.