Ocular infections associated with atypical mycobacteria: A review.

Atypical mycobacteria or non-tuberculous mycobacteria (NTM) are a group of acid-fast bacteria that are pathogenic to different parts of the eye. The organisms can cause a spectrum of ocular infections including keratitis, scleritis, uveitis, endophthalmitis and orbital cellulitis. Trauma, whether surgical or nonsurgical, has the highest correlation with development of this infection. Common surgeries after which these infections have been reported include laser in situ keratomileusis (LASIK) and scleral buckle surgery. The organism is noted to form biofilms with sequestration of the microbe at different inaccessible locations leading to high virulence. Collection of infective ocular material (corneal scraping/necrotic scleral tissue/abscess material/vitreous aspirate, etc.) and laboratory identification of the organism through microbiologic testing are vital for confirming presence of the infection and initiating treatment. In cluster infections, tracing the source of infection in the hospital setting via testing of different in-house samples is equally important to prevent further occurrences. Although the incidence of these infections is low, their presence can cause prolonged disease that may often be resistant to medical therapy alone. In this review, we describe the various types of NTM-ocular infections, their clinical presentation, laboratory diagnosis, management, and outcomes.

Active-site molecular docking of nigellidine with nucleocapsid-NSP2-MPro of COVID-19 and to human IL1R-IL6R and strong antioxidant role of Nigella sativa in experimental rats.

The recent outbreak of SARS CoV-2 has changed the global scenario of human lives/economy. A significant number of the non-survivors showed cardiac renal vasculature dysfunction. A 'cytokine storm' namely, interleukin IL6-IL1 receptors, i.e. IL6R-IL1R over-functioning was reported. Here, nigellidine, an indazole alkaloid and key component of Nigella sativa L. (NS) commonly known as black cumin seed was analysed for COVID-19 protein targeting and IL1R-IL6R inhibition through molecular docking study and biochemical study in experimental rat to evaluate antioxidative capacity. The NMR/X-ray crystallographic/electron microscopic structures of COVID-19 main protease (6LU7)/spike glycoprotein (6vsb)/NSP2 (QHD43415_2)/nucleocapsid (QHD43423), human IL1R (1itb)-IL6R (1pm9) from PDB were retrieved analysed for receptor-ligand interaction. Then, those structures were docked with nigellidine using AutoDock and PatchDock server. A brief comparison was made with nigellicine thymoquinone from N. sativa. Where nigellidine showed highest binding energy of -6.6 kcal/mol, ligand efficiency of -0.3 with COVID19 Nsp2 forming bonds with amino acid CYS240 present in binding pocket. Nigellidine showed strong interaction with main protease (BE: -6.38/LE: -0.29). Nigellidine showed affinity to IL1R (-6.23). The NS treated rat showed marked decline in ALP-SGPT-SGOT-malondialdehyde (MDA) than the basal levels. From the Western blot and activity analysis, it was observed that Nigellidine (sulphuryl group drug) showed no impact on phenol-catalysing ASTIV and steroid-catalysing oestrogen-sulphotransferase expressions and activities in liver tissue and thus has no influence in sulphation-mediated adverse metabolic processes. Conclusively, nigellidine has hepato-reno-protective/antioxidant-immunomodulatory/anti-inflammatory activities with inhibit potentials of COVID-19 proteins. Further validation is necessary.

Early postoperative infection following lamellar keratoplasty: a review.

With the growing popularity of lamellar keratoplasty for selective replacement of diseased corneal tissue, it is important to understand the risk of developing an infection after the procedure. Although lesser than that postpenetrating keratoplasty, the reports on post lamellar keratoplasty infectious keratitis are not negligible. Trends of acute infections arising within 2 months of surgery are a subject of interest. Most of these infections are reported post Descemet's stripping endothelial keratoplasty with a preponderance of Candida species. A donor to host transmission of infection is not uncommon. Among the Candida cases, about 80% seem to occur due to a donor to host transmission. Infections presenting as or progressing to endophthalmitis lead to a poor visual outcome. Strict aseptic measures and protocols during corneal tissue harvesting, tissue processing, tissue storage and surgery are essential to prevent occurrence of these infections. After the infection has occurred, determining the aetiology and drug susceptibility through microbiological testing is vital. This helps to guide treatment protocols and hence determines final outcome of these cases. Most cases require some form of surgical management for resolution of infection, most often a graft removal and therapeutic keratoplasty. Secondary surgical interventions are performed to restore graft clarity and achieve a good final visual outcome.

Antimicrobial loaded gum odina - gelatin based biomimetic spongy scaffold for accelerated wound healing with complete cutaneous texture.

The main objective of this study was to assess the therapeutic activity of gum odina and gelatin based biomimetic scaffold which was previously established as an excellent wound dressing material. In the accelerated stability study, the changes in physicochemical properties were found to be negligible. The cytotoxicity studies were carried out in-vitro and the results showed that upto 90% of the cells remained viable in presence of the scaffold, confirming its biocompatibility. Moreover, results depicted the superior ability of the scaffold to promote cutaneous healing by increasing the rate of wound contraction (about 98%), granulation formation, collagen deposition and formation of an intact epidermis within 18 days. A satisfactory amount of hydroxyproline (240.2 ± 6.67 µg/100 mg tissue) in scaffold treated groups at 21 days ensured the significant deposition of collagen to re-epithelialization. Further it can be hypothesized that the controlled levels of antioxidant enzymes (SOD, CAT) to diminish the oxidative stress in the wounded sites were due to the innate antioxidant properties of both blank and drug loaded scaffold. These results strongly indicated that the prepared scaffolds have strong potential for biomedical applications and it may serve as promising candidate for the next generation of wound treatment systems.

Keratitis following laser refractive surgery: Clinical spectrum, prevention and management.

Laser refractive surgery (LRS) is one of the most demanding areas of ophthalmic surgery and high level of precision is required to meet outcome expectations of patients. Post-operative recovery is of vital importance. Keratitis occurring after LRS can delay visual recovery. Both surface ablations [Photorefractive keratectomy (PRK)] as well as flap procedures [Laser in-situ keratomileusis (LASIK)/Small incision lenticule extraction] are prone to this complication. Reported incidence of post-LRS infectious keratitis is between 0% and 1.5%. The rate of infections after PRK seems to be higher than that after LASIK. Staphylococci, streptococci, and mycobacteria are the common etiological organisms. About 50-60% of patients present within the first week of surgery. Of the non-infectious keratitis, diffuse lamellar keratitis (DLK) is the most common with reported rates between 0.4% and 4.38%. The incidence of DLK seems to be higher with femtosecond LASIK than with microkeratome LASIK. A lot of stress is laid on prevention of this complication through proper case selection, asepsis, and use of improved protocols. Once keratitis develops, the right approach can help resolve this condition quickly. In cases of suspected microbial keratitis, laboratory identification of the organism is important. Most lesions resolve with medical management alone. Interface irrigation, flap amputation, collagen cross-linking and therapeutic penetrating keratoplasty (TPK) are reserved for severe/non-resolving cases. About 50-75% of all infectious keratitis cases post LRS resolve with a final vision of 20/40 or greater. Improved awareness, early diagnosis, and appropriate intervention can help limit the damage to cornea and preserve vision.

Acute endophthalmitis after penetrating and endothelial keratoplasty at a tertiary eye care center over a 13-year period.

PURPOSE: To evaluate the clinico-microbiological profile, donor cornea risk factors, and outcomes of postkeratoplasty endophthalmitis at a tertiary care center. METHODS: Retrospective analysis of charts of 28 consecutive patients (28 eyes) of acute endophthalmitis following either an endothelial keratoplasty (EK) or an optical penetrating keratoplasty (PK) surgery, performed between 2006 and 2018 (13-year period). Positive microbiology, identification and classification of predisposing factors, surveillance of utilized paired donors, treatment outcomes, and differences in the rate and severity of the event between optical penetrating and endothelial keratoplasty. RESULTS: The estimated incidence of endophthalmitis was 0.23% in the entire cohort; it was 0.34% and 0.15%, after EK and PK, respectively (P = 0.049). The median time of endophthalmitis was 4.5 days postsurgery. Donor-related endophthalmitis was recognized in 7/28 (25%) eyes. Culture positivity was 68% (n = 19 of 28). Bacteria was isolated in 84% (n = 16 of 19) instances; Gram-negative bacilli were more common (87.5%; 14 of 16), and Pseudomonas species (50%; 7 of 14) was the most common Gram-negative bacterium. Majority (>75%) of the Gram-negative bacteria were resistant to all fluoroquinolones, aminoglycosides, 3rd generation cephalosporins, and meropenam; 1/3rd were resistant to imipenem; and 90% were sensitive to colistin. Treatment included intraocular antibiotic injections (96.4%), vitrectomy (42.9%), and therapeutic keratoplasty (50%). In 85.7% (24 of 28), globe was salvaged. The final vision was 20/200 or better in 39.1% (9 of 23) eyes. CONCLUSION: EK carried a higher risk of endophthalmitis than PK in this cohort. Bacterial infection was more common in this series, with Gram negative bacilli being the commonest organisms. Multidrug resistance was common (~75%) in Gram negative isolates.

Clinical and Histopathological Evaluation of a Rabbit Model for Pythium insidiosum Keratitis.

Purpose: To describe the clinical characteristics and histopathological features in a rabbit model of Pythium insidiosum keratitis.Methods: Zoospores of P. insidiosum isolated from a patient with microbial keratitis were used for inoculation of the right eye of 48 New Zealand White rabbits in either low (LD) or high dose (HD). Apart from variable dosage the rabbits were grouped (6 rabbits per group) based on route of inoculation (topical on abraded cornea or intracorneal) and immunosuppression (subconjunctival steroid or no steroid). Left eye received phosphate buffered saline via route similar to the right eye. Daily clinical examination of the eye was done, the corneas were harvested on day 3, 7 and 9 and part of the cornea was preserved in 10% neutral buffered formalin for histopathological examination.Results: Left eye of all rabbits were clinically normal. Eyes with intracorneal injection of zoospores developed infection irrespective of dose of inoculation and administration of steroids. One of the consistent early signs of infection was ring like infiltrate in the peripheral cornea. On day 2, rabbits receiving HD developed significantly greater inflammation compared to LD [median clinical score in HD- 11 (IQR = 10-12), versus 9 (IQR = 8-9) in LD (p = 0.004)]. The density of inflammation showed temporal correlation (increase with time) when the inoculum was low. Of the rabbits that received topical inoculation one rabbit cornea showed mild infiltrate in steroid group while no eye was infected in the group without steroid. Sparsely septate to aseptate branching filaments were noted in the stroma of all infected corneas.Conclusions: We describe the first animal model of Pythium keratitis that holds promise for future studies. While topical inoculation of zoospores was unsuccessful in causing infection intracorneal inoculation without immunosuppression was sufficient to develop clinically severe keratitis in rabbits.

Successful management of bullous pemphigoid with dimethyl fumarate therapy: A case report.

A 69-year-old woman affected by multiple sclerosis for 35 years was diagnosed with bullous pemphigoid (BP) and treated successfully with dimethyl fumarate (DMF) at a dose of 120 mg twice per day for 7 days and then increased to 240 mg twice per day after first-line therapies of BP. DMF is now under evaluation with an investigator-initiated prospective controlled trial in patients with BP to determine the efficacy and safety of adjuvant DMF. To our knowledge, this is the first case of BP successfully treated with DMF in the literature.

Cataract surgery in ocular surface diseases: clinical challenges and outcomes.

PURPOSE OF REVIEW: Cataracts are a significant cause of blindness and visual impairment worldwide. With the recent advances in cataract surgery techniques, outcomes have improved significantly in uncomplicated cases. This article discusses the challenges and outcomes of cataract surgery in complex cases targeting eyes with ocular surface diseases like Stevens-Johnson syndrome, ocular cicatricial pemphigoid, Mooren's ulcer, vernal keratoconjunctivitis and limbal stem cell deficiency. RECENT FINDINGS: Ocular surface diseases are commonly associated with corneal scarring and vascularization, conjunctival inflammation, symblepharon and forniceal shortening. Any surgical intervention in a hostile ocular surface environment may worsen the disease, which may result in visual deterioration. In recent past, with the use of immunosuppressants and with the introduction of different ocular surface reconstruction surgeries; stabilization of ocular surface can be achieved prior to planning cataract surgery. This kind of step-wise approach can considerably improve visual outcomes in such cases. SUMMARY: Cataract surgery in ocular surface diseases needs careful preoperative, intraoperative and postoperative planning. Performed in a staged manner under favorable ocular environment, it has good visual outcomes and can improve the quality of life in such patients.

Clinical course and outcomes in patients with Mooren ulcer who had cataract surgery.

PURPOSE: To report outcomes of cataract surgery in patients with Mooren ulcer. SETTING: L.V. Prasad Eye Institute, Hyderabad, India. DESIGN: Retrospective case series. METHODS: The medical records of patients with Mooren ulcer who had cataract surgery between 2000 and 2015 were assessed. The main outcome measures were the role of preoperative immunosuppression and disease inactivity, cataract surgery safety, visual outcomes, and postoperative ulcer recurrence. RESULTS: Of 22 patients (26 eyes), the mean corneal ulceration was 6.8 clock hours ± 2.9 (SD). Corticosteroids were the most commonly used (84.6% of the 26 eyes) preoperative immunosuppression agents and 38.5% of the 26 eyes were under maintenance immunosuppression. The median disease inactivity before surgery was 7 months. Cataract surgery was extracapsular in 10 patients, small incision in 3 patients, and phacoemulsification in 13 patients. Twenty-two eyes had scleral incisions. The median follow-up was 6 months (interquartile range, 10 months). The median corrected distance visual acuity (CDVA) improved from 1.48 logarithm of minimum angle of resolution (logMAR) before surgery to 0.30 and 0.35 logMAR at 1 month and at the last follow-up after surgery, respectively (P ≤ .0001). Mooren ulcer recurred in 5 eyes between 3 months and 7 years after surgery. No disease activity was seen in the immediate postoperative period. No significant risk factors for disease recurrence were noted. CONCLUSIONS: With adequate immunosuppression, cataract surgery in eyes with Mooren ulcer was safe and CDVA improved significantly with no disease reactivation immediately after surgery. No proven role of maintenance immunosuppression was observed. The type of cataract surgery had no influence on ulcer reactivation. Patients with a disease-free interval of 6 months or more before surgery and those who had scleral incisions had favorable outcomes.

Vernal keratoconjunctivitis: culmination of management using immunosuppression, surgical and prosthetic therapy over quarter century.

A 22-year-old male patient presented in 1988 with active vernal keratoconjunctivitis. He was treated with topical mast cell stabilisers and corticosteroids. Chronic inflammation despite topical treatment necessitated oral immunosuppressants. Active disease came under control with this; however, the patient gradually developed limbal stem cell deficiency. He underwent bilateral pannus resection with amniotic membrane transplantation that resulted in improved ocular surface. In 2007, patient was found to have significant bilateral posterior subcapsular cataracts and underwent bilateral cataract surgery with intraocular lens implantation with good visual outcome. In 2016, he was provided with scleral lens prosthetic device, which further improved vision. At last follow-up, more than 25 years after his initial visit, his visual acuity was 20/25 in both eyes with a stable surface. With a comprehensive approach using immunosuppression, surgical therapy and scleral lens prosthetic device, chronic vernal keratoconjunctivitis can be well managed as illustrated in this case.

Cytoprotective and Antioxidant Effects of an Edible Herb, Enhydra fluctuans Lour. (Asteraceae), against Experimentally Induced Lead Acetate Intoxication.

BACKGROUND: Enhydra fluctuans Lour. (Asteraceae), an edible aquatic herb, is traditionally employed against toxic effects of heavy metals in India. The present study was planned to discover the protective effect of edible extract of E. fluctuans (AEEF) against Pb toxicity. METHODS: The cytoprotective role of AEEF was determined on murine hepatocytes employing MTT assay and Hoechst staining. The effects on lipid peroxidation, protein carbonylation, endogenous redox systems and the transcription levels of apoptotic proteins were studied after incubating the hepatocytes with AEEF (400 µg/ml) + Pb-acetate (6.8 µM). The defensive role of AEEF (100 mg/kg) against Pb-acetate (5 mg/kg) intoxication was measured in mice by in vivo assays. Biochemical, haematological and histological parameters, intracellular Pb burden and redox status were measured. RESULTS: AEEF exhibited a concentration dependent cytoprotective effect against Pb-induced cytotoxicity in vitro. Pb-acetate incubation significantly (p < 0.01) altered the extents of ROS production ↑, protein carbonylation ↑, lipid peroxidation ↑, endogenous antioxidant enzymes ↓ and GSH ↓ in vitro. Besides, Pb-acetate significantly (p < 0.01) induced apoptosis in the hepatocytes apparent from the altered expressions of apoptotic proteins viz. Apaf-1 ↑, Bad ↑, Bcl-2 ↓, Cyt C ↑, cleaved caspases↑, Bid ↑ and Fas ↑. However, AEEF (400 µg/ml) could significantly (p < 0.05-0.01) attenuate the Pb-acetate mediated toxic manifestation in vitro. In in vivo assay, Pb-acetate (5 mg/kg) treated mice exhibited significantly (p < 0.01) high intracellular Pb content. A high Pb-burden within the tissues caused significant (p < 0.05-0.01) patho-physiological alterations viz. ROS production ↑, protein carbonylation↑, lipid peroxidation ↑, DNA fragmentation ↑, ATP formation ↑, mitochondrial co-enzymes Q ↓, endogenous antioxidant enzymes ↓ and GSH ↓ within the selected tissues. The haematological and serum biochemical parameters were significantly (p < 0.05-0.01) different in the Pb-acetate treated mice. Finally, histological assessment imposed significant toxic occurrence within the organs of Pb-intoxicated animals. However, concurrent administration of AEEF (100 mg/kg) could significantly (p < 0.05-0.01) reinstate the Pb-acetate mediated toxicity. CONCLUSION: Presence of metal chelators and phyto-antioxidants within AEEF would offer overall protection through promoting Pb clearance coupled with restoring redox balance.

Water Spinach, Ipomoea aquatic (Convolvulaceae), Ameliorates Lead Toxicity by Inhibiting Oxidative Stress and Apoptosis.

BACKGROUND: Ipomoea aquatica (Convolvulaceae), an aquatic edible plant, is traditionally used against heavy metal toxicity in India. The current study intended to explore the protective role of edible (aqueous) extract of I. aquatica (AEIA) against experimentally induced Pb-intoxication. METHODS: The cytoprotective role of AEIA was measured on mouse hepatocytes by cell viability assay followed by Hoechst staining and flow cytometric assay. The effect on ROS production, lipid peroxidation, protein carbonylation, intracellular redox status were measured after incubating the hepatocytes with Pb-acetate (6.8 µM) along with AEIA (400 µg/ml). The effects on the expressions of apoptotic signal proteins were estimated by western blotting. The protective role of AEIA was measured by in vivo assay in mice. Haematological, serum biochemical, tissue redox status, Pb bioaccumulation and histological parameters were evaluated to estimate the protective role of AEIA (100 mg/kg) against Pb-acetate (5 mg/kg) intoxication. RESULTS: Pb-acetate treated hepatocytes showed a gradual reduction of cell viability dose-dependently with an IC50 value of 6.8 µM. Pb-acetate treated hepatocytes exhibited significantly enhanced levels (p < 0.01) of ROS production, lipid peroxidation, protein carbonylation with concomitant depletion (p < 0.01) of antioxidant enzymes and GSH. However, AEIA treatment could significantly restore the aforementioned parameters in murine hepatocytes near to normalcy. Besides, AEIA significantly reversed (p < 0.05-0.01) the alterations of transcription levels of apoptotic proteins viz. Bcl 2, Bad, Cyt C, Apaf-1, cleaved caspases [caspase 3, caspase 8 and caspase 9], Fas and Bid. In in vivo bioassay, Pb-acetate treatment caused significantly high intracellular Pb burden and oxidative pressure in the kidney, liver, heart, brain and testes in mice. In addition, the haematological and serum biochemical factors were changed significantly in Pb-acetate-treated animals. AEIA treatment restored significantly the evaluated-parameters to the near-normal position. CONCLUSION: The extract may offer the protective effect via counteracting with Pb mediated oxidative stress and/or promoting the elimination of Pb by chelating. The presence of substantial quantities of flavonoids, phenolics and saponins would be responsible for the overall protective effect.

Molten metal ocular burn: long-term outcome using simple limbal epithelial transplantation.

One day after molten aluminium had fallen into his right eye, a young man presented to our clinic with a vision of counting fingers at 1 m, conjunctival and corneal epithelial defects, and limbal involvement. He was diagnosed with grade 4 thermal burn and managed medically. Subsequently, the inflammation resolved, however, he developed pannus with conjunctivalisation and scarring of cornea suggestive of partial unilateral limbal stem cell deficiency. He was treated surgically with autologous simple limbal epithelial transplantation (SLET). Postoperatively, his vision improved along with corneal clarity. He achieved a best corrected vision of 20/50 at the last follow-up 27 months postsurgery, with maintenance of a healthy corneal epithelium. This case describes the different management strategies employed in two different stages of an ocular burn. It highlights the long-term success of SLET in a case of ocular surface thermal burn.