Cytokine Levels in Experimental Branch Retinal Vein Occlusion Treated With Either Bevacizumab or Triamcinolone Acetonide.

Purpose: To compare gene expression changes following branch retinal vein occlusion (BRVO) in the pig with and without bevacizumab (BEV) and triamcinolone acetonide (TA). Methods: Photothrombotic BRVOs were created in both eyes of four groups of nine pigs (2, 6, 10, and 20 days). In each group, six pigs received intravitreal injections of BEV in one eye and TA in the fellow eye, with three pigs serving as untreated BRVO controls. Three untreated pigs served as healthy controls. Expression of mRNA of vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), dystrophin (DMD), potassium inwardly rectifying channel subfamily J member 10 protein (Kir4.1, KCNJ10), aquaporin-4 (AQP4), stromal cell-derived factor-1α (CXCL12), interleukin-6 (IL6), interleukin-8 (IL8), monocyte chemoattractant protein-1 (CCL2), intercellular adhesion molecule 1 (ICAM1), and heat shock factor 1 (HSF1) were analyzed by quantitative reverse-transcription polymerase chain reaction. Retinal VEGF protein levels were characterized by immunohistochemistry. Results: In untreated eyes, BRVO significantly increased expression of GFAP, IL8, CCL2, ICAM1, HSF1, and AQP4. Expression of VEGF, KCNJ10, and CXCL12 was significantly reduced by 6 days post-BRVO, with expression recovering to healthy control levels by day 20. Treatment with BEV or TA significantly increased VEGF, DMD, and IL6 expression compared with untreated BRVO eyes and suppressed BRVO-induced CCL2 and AQP4 upregulation, as well as recovery of KCNJ10 expression, at 10 to 20 days post-BRVO. Conclusions: Inflammation and cellular osmohomeostasis rather than VEGF suppression appear to play important roles in BRVO-induced retinal neurodegeneration, enhanced in both BEV- and TA-treated retinas. Translational Relevance: Inner retinal neurodegeneration seen in this acute model of BRVO appears to be mediated by inflammation and alterations in osmohomeostasis rather than VEGF inhibition, which may have implications for more specific treatment modalities in the acute phase of BRVO.

The Fight Tumour Blindness Registry: Efficient capture of high-quality real-world data in uveal melanoma.

OBJECTIVE: To describe the development of a web-based data collection tool to track the management and outcomes of uveal melanoma patients. DESIGN: Description of a clinical registry. PARTICIPANTS: Patients with uveal melanoma. METHODS: A panel of expert ocular oncologists, with input from other relevant specialties and individuals with expertise in registry development, collaborated to formulate a minimum data set to be collected to track patient centred, real-world outcomes in uveal melanoma. This data set was used to create the Fight Tumour Blindness! (FTB!) registry within Save Sight Registries. RESULTS: The data set to be collected includes patient demographics and medical history, baseline visit, follow-up visit including tumour treatment, metastatic staging and surveillance, pathology, and patient-reported questionnaires. The inbuilt mechanisms to ensure efficient and complete data collection are described. CONCLUSIONS: The FTB! registry can be used to monitor outcomes for patients with uveal melanoma. It allows benchmarking of outcomes and comparisons between different clinics and countries.

Inner Retinal Changes in Acute Experimental BRVO Treated With Bevacizumab or Triamcinolone Acetonide.

Purpose: Apoptosis is a key process in neural degeneration associated with retinal vascular diseases. Vascular endothelial growth factor (VEGF) antagonists, including bevacizumab, are used to treat macular edema in these diseases. As VEGF has a critical role in the preservation of retinal neuronal cells, this study investigates the effects of bevacizumab on neural damage in a pig model of branch retinal vein occlusion (BRVO) and compares it with triamcinolone acetonide (TA) which is reported to possess neuroprotective properties. Methods: Thirty-six pigs had a photothrombotic BRVO in both eyes. Six pigs were injected with bevacizumab in one eye and TA in the fellow eye, then they were sacrificed, the eyes enucleated, and retinas processed at 2, 6, 10, and 20 days, respectively, together with three pigs (six eyes) BRVO only and three normal pigs (six eyes). Neuronal degeneration (apoptosis) and associated inner retinal changes were determined by terminal deoxyynuclotidyl transferase dUTP nick-end labeling (TUNEL), histology, and immunohistochemistry for macrophages. Results: TUNEL labeling showed significantly higher apoptosis rates in the ganglion cell layer (GCL) and the inner nuclear layer (INL) in the bevacizumab-treated compared with the TA-treated retinas at 2, 10, and 20 day time points after occlusion (P < 0.05). Pyknotic cells were significantly higher in the GCL in bevacizumab-treated eyes at 6, 10, and 20 days and in the INL at 2 days compared to TA-treated retinas (P < 0.05). Macrophage infiltration was seen at all time points in both untreated and treated retinas with an absence of significance between bevacizumab- and TA-treated retinas (P > 0.05). Conclusions: Neurodegeneration in the BRVO acute phase is exacerbated by current standard treatments for BRVO. These results may have implications for the timing and treatment type. Translational Relevance: In the acute phase of BRVO, VEGF suppression with bevacizumab and to a lesser extent with triamcinolone exacerbates apoptosis in the inner retinal layers, which has implications for both the timing and choice of treatment.

Better visual outcome associated with early vitrectomy in the management of endophthalmitis.

AIMS: To examine the role of early vitrectomy in the management of endophthalmitis from all causes. METHODS: Retrospective study of 290 consecutive subjects diagnosed with endophthalmitis at Auckland District Health Board between 1 January 2006 and 31 July 2019. Main outcome measure was visual acuity at 9-month follow-up and proportion of subjects with severe vision loss (≤20/200). RESULTS: Median age at presentation was 70.4 years and 151 subjects (52.1%) were women. Cataract surgery was the most common cause of endophthalmitis in 92 subjects (31.7%) followed by intravitreal injection in 57 (19.7%), endogenous endophthalmitis in 48 subjects (16.6%), non-surgical trauma in 42 subjects (14.5%), glaucoma surgery in 24 subjects (8.3%), vitrectomy in 22 subjects (7.6%) and corneal in 5 subjects (1.7%). Culture was positive in 136 (46.9%) with gram-positive organisms most common (76.5%). Early vitrectomy was performed in 82 subjects (28.3%). Median visual acuity at 9 months was 20/100 (IQR 20/30 to light perception), and severe vision loss occurred in 100 (43.5%). Retinal detachment occurred in 35 eyes (12.1%) and 26 eyes were enucleated. On multivariate analysis, younger age, poor presenting visual acuity and culture-positive endophthalmitis were associated with worse outcomes, and early vitrectomy was associated with better outcomes. CONCLUSIONS: Early vitrectomy (within 24 hours) is associated with better visual outcomes at 9 months, while younger age, poor presenting visual acuity and culture-positive endophthalmitis are associated with poorer visual acuity outcomes.

Serratia Marcescens Endophthalmitis and Bacteraemia following Complicated Cataract Surgery.

A 93-year-old male presented with left eye pain, fever and loss of vision two days after complicated cataract surgery. A diagnosis of Serratia marcescens endophthalmitis and systemic bacteremia was made after the organism was identified on vitreous and peripheral blood cultures. This case demonstrates that an aggressive intraocular infection can lead to bacteremia.

Analysis of Circulating Tumour Cells in Early-Stage Uveal Melanoma: Evaluation of Tumour Marker Expression to Increase Capture.

(1) Background: The stratification of uveal melanoma (UM) patients into prognostic groups is critical for patient management and for directing patients towards clinical trials. Current classification is based on clinicopathological and molecular features of the tumour. Analysis of circulating tumour cells (CTCs) has been proposed as a tool to avoid invasive biopsy of the primary tumour. However, the clinical utility of such liquid biopsy depends on the detection rate of CTCs. (2) Methods: The expression of melanoma, melanocyte, and stem cell markers was tested in a primary tissue microarray (TMA) and UM cell lines. Markers found to be highly expressed in primary UM were used to either immunomagnetically isolate or immunostain UM CTCs prior to treatment of the primary lesion. (3) Results: TMA and cell lines had heterogeneous expression of common melanoma, melanocyte, and stem cell markers. A multi-marker panel of immunomagnetic beads enabled isolation of CTCs in 37/43 (86%) patients with UM. Detection of three or more CTCs using the multi-marker panel, but not MCSP alone, was a significant predictor of shorter progression free (p = 0.040) and overall (p = 0.022) survival. (4) Conclusions: The multi-marker immunomagnetic isolation protocol enabled the detection of CTCs in most primary UM patients. Overall, our results suggest that a multi-marker approach could be a powerful tool for CTC separation for non-invasive prognostication of UM.

Factors Associated With Positive Microbial Culture in Patients With Endophthalmitis Based on Clinical Presentation and Multimodal Intraocular Sampling.

PURPOSE: The aim of this study was to identify the factors associated with positive culture sample in patients with endophthalmitis based on clinical presentation and multimodal intraocular sampling. DESIGN: Retrospective review. METHODS: A total of 259 subjects with a diagnosis of endophthalmitis presented to a tertiary ophthalmic referral center between 2006 and 2018. Patient demographics, presenting clinical findings and the results of aqueous and vitreous sampling were analyzed. RESULTS: Mean age was 64.2 (± 22.6) years with 52.9% female. Endophthalmitis followed cataract surgery in 84 eyes (32.4%) and was the most common precipitant; intravitreal injections were the next common cause involving 60 eyes (23.2%). Mean visual acuity on presentation was hand movements with a hypopyon present 134 eyes (52%). In total, 135 cases (52.1%) were culture positive. Aqueous sampling was performed in 112 eyes [culture positive 36 (32.1%)]; vitreous sample in 122 eyes [positive in 56 (45.3%)]. Vitrectomy was performed in 169 eyes with 149 sent for culture [70 (47.0%) positive]. A positive vitrectomy culture was observed in 14 eyes (36.9%) of 38, despite initial treatment with intravitreal antibiotics. Factors associated with positive culture were aqueous tap [odds ratio (OR) 2.06, P = 0.02], vitrectomy (OR 2.86, P = 0.001), and absent red reflex (OR 2.73, P = 0.001). CONCLUSIONS: A multimodal approach to intraocular sampling should be considered in those presenting with endophthalmitis, with both aqueous tap and vitrectomy associated with an increased probability of achieving a positive culture.

Primary Ocular Toxoplasmosis Presenting to Uveitis Services in a Non-endemic Setting.

PURPOSE: This study sought to describe the different clinical features and presentations of primary ocular toxoplasmosis in a setting not demonstrating an outbreak of disease. METHODS: This was a retrospective review of patients presenting to uveitis management services in Auckland and Hamilton, New Zealand between 2003 to 2018 with uveitis and positive toxoplasmosis immunoglobulin M serology. RESULTS: We identified 16 patients with primary acquired toxoplasmosis infection and ocular involvement. The mean age was 53 years. Systemic symptoms were reported in 56% (9 / 16). Visual acuity was reduced to 20 / 30 or less in 50% of patients (8 / 16). A single focus of retinitis without a pigmented scar was the salient clinical feature in 69% (11 / 16). Optic nerve inflammation was the sole clinical finding in 19% (3 / 16). Bilateral arterial vasculitis was the sole clinical finding in 13% (2 / 16). A delay in the diagnosis of toxoplasmosis of more than two weeks occurred in 38% (6 / 16) due to an initial alternative diagnosis. Antibiotic therapy was prescribed in all cases. Vision was maintained or improved in 69% (11 / 16) at the most recent follow-up visit (15 months to 10 years). Relapse occurred in 69% (11 / 16), typically within four years from the initial presentation. CONCLUSIONS: Primary ocular toxoplasmosis presenting in adulthood is a relatively uncommon cause of posterior uveitis in New Zealand. This condition should be considered in any patient presenting with retinitis or optic nerve inflammation without a retinochoroidal scar. This disease tends to relapse; thus, close follow-up is required.

Subtenon Bupivacaine for Postoperative Pain in Patients Undergoing Pterygium Excision: A Double-Blinded Randomized Control Trial.

PURPOSE: Patients undergoing primary pterygium excision with autologous conjunctival autograft and human tissue adhesive in New Zealand, currently receive subconjunctival anesthesia with oral postoperative analgesia for pain. Our aim was to investigate the potential added benefit of intraoperative subtenon bupivacaine to this regimen. METHODS: A double-blinded, placebo-controlled, randomized trial was conducted at 2 centers. All patients received topical and subconjunctival anesthesia intraoperatively, with standardized oral analgesia as required postoperatively. Participants were allocated to receive subtenon bupivacaine 0.5% or placebo at the conclusion of surgery. Corneal epithelial defect and conjunctival graft size were recorded. Pain and ocular surface irritation were assessed (Likert scale) immediately postoperatively at 3, 6, 12, 24, and 36 hours. Cumulative oral analgesia consumption (doses) was reported at 24 and 36 hours. RESULTS: Forty-two patients were randomized with participants evenly matched at baseline. Postoperative pain at all time points ≤24 hours was significantly less (2.4 vs. 1.2; P < 0.04) in the bupivacaine arm with no difference at 36 hours (P = 0.27). Ocular surface irritation was also significantly less at all time points ≤12 hours (4.8 vs. 1.3; P < 0.01) with no difference at 24 hours (P = 0.10). Analgesia consumption was less in the bupivacaine arm at 24 (6.5 vs. 2.5; P < 0.01) and 36 hours (7.6 vs. 3.4; P < 0.01). No complications were observed. CONCLUSIONS: Intraoperative subtenon bupivacaine improves patient comfort after pterygium excision by reducing pain, irritation, and requirement for oral analgesia after surgery.

Improved Refractive Outcomes of Small-Incision Extracapsular Cataract Surgery after Implementation of a Biometry Training Course.

PURPOSE: To determine whether a biometry training course could improve refractive outcomes of patients undergoing manual small-incision extracapsular cataract surgery (SICS). MATERIALS AND METHODS: This was a prospective, interventional, cohort study at the Pacific Eye Institute, Fiji. SICS refractive outcomes were evaluated before and after a structured biometry teaching course. Eyes that underwent evaluation and subsequent SICS with placement of a posterior chamber intraocular lens (IOL) were included. Axial length measurements were obtained using A-scan applanation ultrasound and keratometry with a handheld keratometer. Main outcome measures included mean absolute prediction error of IOL calculations, percentage of eyes within ±0.5 D and ±1.0 D of intended spherical equivalent, and proportion of eyes with ≥6/18 uncorrected visual acuity. RESULTS: A total of 240 eyes were analyzed: 120 eyes before and 120 eyes after the structured biometry training. The mean absolute prediction error was 50% lower following the training (1.13 ± 0.84 D pre vs. 0.56 ± 0.44 D post; P < 0.001). A higher percentage of the eyes had a postoperative spherical equivalent within ±0.5 D (26.7% pre vs. 52.5% post; P < 0.001) and ±1.0 D (55.0% pre vs. 90.0% post; P < 0.001) of the intended target. A higher proportion of the eyes achieved ≥6/18 uncorrected visual acuity (77.5% pre vs. 91.7% post, P = 0.004), while the proportion with ≥6/18 corrected visual acuity was similar (94.4% pre vs. 98.3% post; P = 0.28). CONCLUSIONS: A structured biometry training course may improve the accuracy of preoperative IOL calculations to achieve the postoperative refractive target. Ophthalmology training programs should include structured biometry teaching in their curricula.

Demographic features and visual outcomes of patients presenting to diabetic photo-screening and treated for sight threatening retinopathy in Fiji.

AIM: To describe the demographic features and visual outcomes of patients presenting to photo-screening services, and treated for sight threatening retinopathy (STR) in a low resource setting, Fiji. METHODS: A retrospective review of all new patients who presented for diabetic photo-screening at the Diabetic Eye Clinic, Suva in 2010. Fundus images were graded using standardised guidelines. Patient demographics, retinopathy grading and visual acuity data were extracted from the database and analyzed. Patients that received laser therapy and still attending follow up in 2012 were examined for disease progression. RESULTS: Totally 2236 patients were photo-screened, 87% (3870/4472) of images were gradable. STR was observed in 26% (988/3870) with advanced STR (proliferative retinopathy/severe maculopathy) in 10% (385/3870). Of those with STR, 59% had BCVA ≥6/18, 31% with advanced STR were <6/60. Male gender [odds ratio (OR) 1.59; 1.20-2.12], history of hypertension (OR 1.36; 1.03-1.80) and peripheral neuropathy (OR 1.41; 1.01-1.95) were predictive of advanced STR. In 2012, 32% (315/988) attended follow up with 69% exhibiting advanced STR compared with 53% of the same cohort in 2010. Laser photocoagulation was administered to 212 eyes (212/3870, 5%) with retinopathy and maculopathy progression observed in 52% and 33% respectively. BCVA ≥6/18 was noted in 67% (143/212) of treated eyes. Improved glycaemic control (OR 46.52; 1.50-1441.90) amongst those with advanced STR was predictive of eyes that maintained good vision. CONCLUSION: In Fiji, a quarter of new patients presenting to photo-screening have STR with a third of those with advanced STR having already loss vision. Improved glycaemic control and timely treatment of patients with sight threatening complications is important in halting disease progression.

Short-term outcomes of small incision cataract surgery provided by a regional population in the Pacific.

BACKGROUND: This study aims to describe patient demographics, visual and surgical outcomes of a cohort undergoing small incision cataract surgery at a Pacific regional ophthalmic training facility. DESIGN: This is a prospective, longitudinal study conducted at the Pacific Eye Institute, Fiji. PARTICIPANTS: One hundred fifty-six patients underwent small incision cataract surgery. METHODS: Preoperatively, a complete ophthalmic examination, including pachymetry and macular optical coherence tomography performed by two independent investigators. Temporal small incision cataract surgery with intraocular lens insertion was performed by ophthalmologists, and trainee ophthalmologists. Follow-up occurred at day one, four weeks and 3 months. MAIN OUTCOME MEASURES: Patient characteristics, visual outcomes including surgically induced astigmatism and complications. RESULTS: Ninety-one per cent (142/156) attended 3-month follow-up with median age 63 years (range 19-82), 52% female (81/156) and 58% (90/156) Fijian ethnicity. In 37% (57/156), the contralateral eye was pseudophakic. Mean preoperative best spectacle-corrected visual acuity was logMAR 1.44 (6/165). At 3 months, 74% (105/142) achieved ≥6/18 unaided vision (94% [133/142] best spectacle-corrected visual acuity). Mean postoperative spherical equivalent was -0.78 (SD 0.95) D and mean surgically induced astigmatism 1.04 (0.57) D. Complications included posterior capsular rupture with vitreous loss (4% [6/156]), optical coherence tomography confirmed macular oedema (8% [12/152] at 4 weeks), significant posterior capsular opacity (23% [31/136]) and >5% increase in preoperative pachymetry (1% [1/142]) at 3 months. Reduction in preoperative best spectacle-corrected visual acuity occurred in 2% (3/142). No cases of endophthalmitis. CONCLUSION AND RELEVANCE: Small incision cataract surgery provided to a regional population is effective with 94% achieving the World Health Organisation's definition of 'Good Vision' (≥6/18). Refinements in biometric and surgical techniques may allow a greater proportion of patients to achieve good unaided vision.