In vivo evaluation of a Nano-enabled therapeutic vitreous substitute for the precise delivery of triamcinolone to the posterior segment of the eye.

This study focused on the design of a thermoresponsive, nano-enabled vitreous substitute for the treatment of retinal diseases. Synthesis of a hydrogel composed of hyaluronic acid and a poloxamer blend was undertaken. Poly(D,L-lactide-co-glycolide) acid nanoparticles encapsulating triamcinolone acetonide (TA) were synthesised with a spherical morphology and mean diameter of ~ 153 nm. Hydrogel fabrication and nanoparticle loading within the hydrogel was confirmed via physicochemical analysis. Gelation studies indicated that hydrogels formed in nine minutes and 10 min for the unloaded and nanoparticle-loaded hydrogels, respectively. The hydrogels displayed in situ gel formation properties, and rheometric viscoelastic studies indicated the unloaded and loaded hydrogels to have modulus values similar to those of the natural vitreous at 37 °C. Administration of the hydrogels was possible via 26G needles allowing for clinical application and drug release of triamcinolone acetonide from the nanoparticle-loaded hydrogel, which provided sustained in vitro drug release over nine weeks. The hydrogels displayed minimal swelling, reaching equilibrium swelling within 12 h for the unloaded hydrogel, and eight hours for the nanoparticle-loaded hydrogel. Biodegradation in simulated vitreous humour with lysozyme showed < 20% degradation within nine weeks. Biocompatibility of both unloaded and loaded hydrogels was shown with mouse fibroblast and human retinal pigment epithelium cell lines. Lastly, a pilot in vivo study in a New Zealand White rabbit model displayed minimal toxicity with precise, localised drug release behaviour, and ocular TA levels maintained within the therapeutic window for the 28-day investigation period, which supports the potential applicability of the unloaded and nanoparticle-loaded hydrogels as vitreous substitutes that function as drug delivery systems following vitrectomy surgery.

Impact of COVID-19 on ophthalmic surgical procedures in sub-Saharan Africa: a multicentre study.

BACKGROUND: The COVID-19 pandemic had a profound impact on healthcare and ophthalmology services globally. Numerous studies amongst various medical and surgical specialties showed a reduction in patient attendance and surgical procedures performed. Prior published ophthalmic literature focused on specific types of procedures and were usually single centre. The current study attempts to quantify the impact on a larger scale, namely that of sub-Saharan Africa, and to include all ophthalmic subspecialties. METHODS: This is a retrospective analysis of the surgical records from 17 ophthalmology centres in seven countries located in East, Central, West and Southern Africa. The date of declaration of the first lockdown was used as the beginning of the pandemic and the pivot point to compare theatre records one year prior to the pandemic and the first year of the pandemic. We examined the total number of surgical procedures over the two year period and categorized them according to ophthalmic subspecialty and type of procedure performed. We then compared the pre-pandemic and pandemic surgical numbers over the two year period. RESULTS: There were 26,357 ophthalmic surgical procedures performed with a significant decrease in the first year of the pandemic (n = 8942) compared to the year prior to the pandemic (n = 17,415). The number of surgical procedures performed was lower in the first year of the pandemic compared to the year prior to the pandemic by 49% [Incidence rate ratio (IRR) 0.51, 95% CI 0.41-0.64), 27% (0.73, 0.55-0.99), 46% (0.54, 0.30-0.99), 40% (0.60, 0.39-0.92) and 59% (0.41, 0.29-0.57) in sub-Saharan Africa (4 regions combined), West, Central, East and Southern Africa, respectively]. The number of surgical procedures in the different sub-specialty categories in sub-Saharan Africa (4 regions combined) was significantly lower in the first year of the pandemic compared to the year prior to the pandemic, except for glaucoma (IRR 0.72, 95% CI 0.52-1.01), oncology (0.71, 0.48-1.05), trauma (0.90, 0.63-1.28) and vitreoretinal (0.67, 0.42-1.08) categories. CONCLUSION: This study provides insight into the impact of the COVID-19 pandemic in multiple regions and countries on the African continent. The identification of which surgical subspecialty was most affected by the COVID-19 pandemic in each region allows for better planning and resource allocation to address these backlogs.

SF 6 COMPARED WITH C 2 F 6 FOR INFERIOR RHEGMATOGENOUS RETINAL REPAIR : The Manchester Pseudophakic Retinal Detachment Study.

PURPOSE: To compare SF 6 relative with C 2 F 6 in the anatomical and functional outcomes following pars plana vitrectomy for uncomplicated primary pseudophakic rhegmatogenous retinal detachment with inferior causative breaks. METHODS: This is a retrospective, comparative study on eyes with pseudophakic rhegmatogenous retinal detachment with inferior causative breaks that had small-gauge pars plana vitrectomy repair using SF 6 and C 2 F 6 tamponade between 2011 and 2020 at a tertiary centre in the United Kingdom. Primary outcome was single surgery anatomical success, and the secondary outcome was best-corrected visual acuity. Propensity score matching, using preoperative findings as covariates to account for relevant confounders, was performed. RESULTS: From 162 pseudophakic rhegmatogenous retinal detachment eyes with inferior causative breaks, the median (interquartile range) follow-up was 82 (52-182) days. The single surgery anatomical success was 156 (96.3%) overall: 47 of 47 (100.0%) and 109 of 115 (94.8%) in the SF 6 and C 2 F 6 groups, respectively ( P = 0.182). Relative to the SF 6 group, the C 2 F 6 group had a higher mean number of tears (SF 6 : 3.1[2.0], C 2 F 6 : 4.5[2.7], P = 0.002) and greater retinal detachment extent (SF 6 : 5.3[2.9], C 2 F 6 : 6.2[2.6] clock hours, P = 0.025). Following propensity score matching analysis, 80 eyes were matched with 40 in each group to homogenize preoperative factors. No significant difference was found in single surgery anatomical success and best-corrected visual acuity between the groups following propensity score matching. CONCLUSION: Primary pars plana vitrectomy with gas tamponade leads to a high single surgery anatomical success rate in uncomplicated pseudophakic rhegmatogenous retinal detachment with inferior causative breaks with no additional benefit associated with long-acting tamponade when comparing C 2 F 6 with SF 6 .

THE LONG-TERM RECOVERY OF VISION IN PSEUDOPHAKIC MACULA-OFF RHEGMATOGENOUS RETINAL DETACHMENTS.

PURPOSE: To assess the long-term visual recovery in uncomplicated macula-off pseudophakic rhegmatogenous retinal detachment treated with pars plana vitrectomy and gas tamponade in the absence of other visual comorbidities. METHODS: Single-center retrospective longitudinal study on eyes with macula-off pseudophakic rhegmatogenous retinal detachment successfully treated with pars plana vitrectomy between 2011 and 2020 and with at least 2 follow-ups (FU), first gas-free FU (first-FU) and a final-FU, were included. Patients with subsequent ocular surgery or comorbidities affecting best-corrected visual acuity were excluded. The duration between operation date and final-FU was calculated (total days FU) and split into total days quintiles-1: ≤57, 2: >57 and ≤77, 3: >77 and ≤152, 4: >152 and ≤508, and 5: >508 days. Multivariable regression was performed with logMAR gain between the first and the final-FU as the dependent variable. RESULTS: In 209 eyes, the authors report association with increase of logMAR gain between the first and the final-FU, with reducing clock hours of pseudophakic rhegmatogenous retinal detachment ( P = 0.041) and relative to the total days Quintile 1. Mean (SD) logMAR gain between the first and the final-FU was 0.02 (0.07) in the first quintile, increasing to 0.14 (0.13) ( P < 0.001) by the fifth quintile on multivariable regression. For patients not achieving 0.30 logMAR at the first-FU, this was attained at the final-FU with a sensitivity of 51.9% and specificity of 95.5% at a cut off ≤0.58 logMAR at the first-FU (area under the curve 0.756 [95% confidence interval 0.664-0.848], P < 0.001). CONCLUSION: The authors report a significant time-dependent visual improvement after uncomplicated pars plana vitrectomy with gas tamponade for macula-off pseudophakic rhegmatogenous retinal detachment without visual confounders and provide important quantitative data for counselling patients with macula-off repair.

The Role of Subretinal Injection in Ophthalmic Surgery: Therapeutic Agent Delivery and Other Indications.

Subretinal injection is performed in vitreoretinal surgery with two main aims, namely, the subretinal delivery of therapeutic agents and subretinal injection of fluid to induce a controlled and localized macular detachment. The growing interest in this technique is mainly related to its suitability to deliver gene therapy in direct contact with target tissues. However, subretinal injection has been also used for the surgical management of submacular hemorrhage through the subretinal delivery of tissue plasminogen activator, and for the repair of full-thickness macular holes, in particular refractory ones. In the light of the increasing importance of this maneuver in vitreoretinal surgery as well as of the lack of a standardized surgical approach, we conducted a comprehensive overview on the current indications for subretinal injection, surgical technique with the available variations, and the potential complications.

Long-Term Safety and Efficacy of Pars Plana Vitrectomy for Uveitis: Experience of a Tertiary Referral Centre in the United Kingdom.

AIM: To evaluate the effectiveness of pars plana vitrectomy (PPV) without macular intervention on uveitis eyes with persistent vitreous inflammation/opacities in terms of visual acuity (VA), intraocular inflammation and macular profile. METHODS: We carried out a single-center retrospective study of patients with uveitic eyes that underwent PPV without intervention on the macula due to persistent vitreous inflammation/opacities. The primary outcome measures were best-corrected visual acuity (BCVA), intraocular inflammation and macular profile at 3, 12 and 24 months after surgery. RESULTS: Twenty-seven eyes of twenty-six patients were analyzed. Overall, 77.8% had an improvement of VA (55% by 0.3 LogMAR or more); 62.5% of patients had no intraocular inflammation, and the number of patients on systemic steroids and second-line immunosuppressives was reduced by 26% at 12 months; 87.5% of patients had resolution of macular oedema at 12 months. CONCLUSION: PPV for persistent vitreous inflammation/opacities is safe and effective, showing beneficial outcomes in terms of improvement of BCVA and the reduction in inflammation.

Response to botulinum neurotoxin injections in large-angle infantile esotropia: a post hoc analysis.

PURPOSE: To determine the anticipated reduction of baseline angle of esotropia and identify predictors of change following botulinum neurotoxin (BNT) injections in large-angle infantile esotropia. METHODS: This was a prospective, longitudinal study of children <10 years of age diagnosed with infantile esotropia of >30Δ and given either 1, 2, or 3 BNT injections. Post-injection change from baseline deviation was recorded, and predictors of reduction were analyzed. For this study, children were further divided into subgroups based on initial deviation of ≤60Δ (group 1) and >60Δ (group 2). The outcomes of subsequent surgeries in failed cases were analyzed. RESULTS: A total of 117 children were included, 55 in group 1 and 62 in group 2. Mean age was 30.3 ± 18.8 months. Mean baseline deviation was 62.5Δ ± 13.1Δ: 51.4Δ ± 8.4Δ in group 1 and 73Δ ± 7.5Δ in group 2. The mean number of injections was 2.2 ± 0.7. Success was achieved in 25.6% of patients (33.4% in group 1; 16.2% in group 2). The mean percentage reduction of deviation after BNT injection was 55.2% ± 26%, larger in group 1 than in group 2 (61.3% vs 51.1% [P = 0.001]). Five children reverted to baseline deviation. In multivariate analysis, adjusting for number of injections, younger age and larger baseline deviation were significant independent predictors of a larger absolute amount of reduction (P = 0.02, and 0.002, resp.). Thirty-two children had subsequent surgery; 22 were followed for a minimum of 6 months, and 20 were aligned within 10Δ of orthotropia. CONCLUSIONS: In large-angle esotropia there was a reduction of approximately 50% of baseline deviation, with greater relative reduction for smaller baseline deviations; the absolute change in angle was greater in younger children. Alignment after subsequent surgery appeared to remain stable and surgery required less recession than would have been needed for the original angle of esotropia.

Tubercular Uveitis in Uveitis Cases in a High TB and HIV Setting: A Prospective Cohort Study.

Purpose: The diagnosis of tubercular uveitis (TBU) is difficult. The lack of a diagnostic gold standard has contributed to challenges in determining the true prevalence and clinical predictors of TBU. We aimed to determine the proportion of TBU cases in adults with uveitis and to examine clinical features associated with TBU. Methods: A prospective cohort study of adult uveitis cases after exclusion of other specific etiologies. The diagnosis of TBU was based on a composite reference of: any clinical signs of uveitis; exclusion of other causes of uveitis; and positive QuantiFERON-Gold test, tuberculin skin test, and/or ocular TB polymerase chain reaction. Results: Of 79 cases analyzed, 49 (62%) had TBU. Female sex (P = 0.001) and chronic uveitis (P = 0.006) cases were more common in the TBU group than the non-TBU group whereas diffuse choroiditis (P = 0.010) and HIV-positive (P = 0.001) cases were less common. Choroidal granulomas (P = 0.176) and serpiginous-like choroiditis (P = 0.292) were more common in TBU group, albeit not significantly. On univariate analysis, female sex (odds ratio, 5.1; P = 0.002), negative HIV status (odds ratio, 0.2; P = 0.001), and chronic uveitis (odds ratio, 4.1; P = 0.008) were associated with TBU. A negative HIV test was associated with TBU on multivariate analysis (P = 0.049). Conclusions: A high proportion of cases had TBU. Our study did not significantly confirm some of the clinical features associated with TBU reported in other studies. Translational Relevance: Our study highlights the difficulties in determining the proportion and clinical predictors of TBU, especially in the absence of a gold standard diagnostic test.

Cost comparison between botulinum neurotoxin and surgery in the treatment of infantile esotropia in a tertiary public hospital.

OBJECTIVE: To compare the cost implications of botulinum neurotoxin (BNT) injection to surgery in infantile esotropia (IE) in a public/government funded hospital. METHODS AND ANALYSIS: A simple costing comparison was undertaken for a randomised clinical trial in IE. Patients were randomised to receive either BNT or standard surgery. The participants in the BNT arm were further subdivided into subgroups based on their age in months and degree of esotropia in prism dioptres (PD) at presentation: G1 ≤60 PD/24 months, G2 ≤24 months/>60 PD, G3 >24 months/≤60 PD, G4 >24 months/>60 PD. The costs were calculated for each arm from primary treatment to eventual satisfactory outcome defined as orthophoria or microtropia (≤10 PD). A bottom-up costing analysis was done for single and multiple procedures for each arm. Comprehensive variable costs as well as fixed costs were calculated at each point of intervention and expressed in local currency ZAR (US$1=ZAR15.00). Costing was analysed for surgery and BNT subgroups (based on clinical success). RESULTS: There were 101 patients enrolled in the trial. 54 in the BNT arm and 47 in the surgery arm. Cost for single surgery and single BNT was ZAR 7743.04 and 1713.14, respectively. A favourable clinical outcome was achieved in 72% of surgery arm and 37% of BNT arm. The mean cost for eventual favourable outcome in BNT arm was ZAR9158.08 and in surgery arm ZAR9124.27 (p=0.26). Mean cost in G1 was ZAR6328.45, in G2 ZAR7197.45, in G3 ZAR11891.93 and G4 ZAR12882.44 (p=0.018). CONCLUSION: BNT has a cost-benefit in IE and is a viable option in the primary treatment of IE in resource constrained regions. Clinical outcomes and economic benefit in smaller angle of esotropia and younger patients are comparable to surgery.

Nodular Posterior Scleritis Masquerading as a Subretinal Mass.

This is the case report of a 50-year-old female with no systemic comorbidities who presented to the eye clinic with a 1-month history of right-sided eye pain and visual loss. Examination revealed no signs of inflammation in the right eye, with no proptosis or conjunctival injection. A relative afferent pupillary defect was present with no inflammatory cells in the vitreous. On fundoscopy, there was a swollen disc, a large superior creamy white subretinal mass associated with a shallow overlying retinal detachment. B-scan ultrasonography confirmed the presence of a subretinal mass. Hematological investigations revealed an elevated erythrocyte sedimentation rate. Infective and autoimmune markers were negative. A diagnosis was made of nodular posterior scleritis and the patient was treated with intravenous corticosteroids initially, and subsequently switched to oral corticosteroids. There was complete resolution of the mass with optic atrophy as a result. Posterior nodular scleritis is an extremely rare potentially vision-threatening ocular condition that requires multimodal investigations to diagnose and treat appropriately.