Landolt Ring-Shaped Epithelial Keratopathy: A Novel Corneal Disease in a Non-Japanese White Patient.

PURPOSE: Landolt ring-shaped epithelial keratopathy is a corneal disease that has only been reported in 11 Japanese patients in 2014.1 We describe the first case of Landolt ring-shaped epithelial keratopathy in the United States in a patient of European background. METHODS: This is a single case report with longitudinal care. RESULTS: A 35-year-old White patient presented with a history of ocular burning, photophobia, and decreased vision. Corneal examination showed bilateral and asymmetric microcystic lesions in a unique Landolt ring (or the letter "C") shape, distributed randomly in the epithelium. Confocal microscopy revealed cellular ballooning and hyperreflective opacities in the basal layer of the corneal epithelium. The patient has had multiple recurrences of her symptoms year-round, each lasting 4 to 8 days. Topical treatment with cyclosporine, steroids, and lubrication resolved her symptoms but without complete resolution of signs on examination. CONCLUSIONS: Our patient's clinical signs and symptoms are similar to those described previously in 11 Japanese patients. However, unlike those patients, our patient demonstrates symptomatic response to topical treatment, no seasonal association to her condition, and to date, incomplete resolution of her disease after more than 2 years. This case highlights that Landolt ring-shaped epithelial keratopathy, a novel corneal disease of unclear origin, has relevance outside of the Japanese population.

Risk of Corneal Graft Rejection and Vaccination: A Matched Case-Control Study From a United States Integrated Health Care System.

PURPOSE: Data on vaccine-associated corneal transplant rejections are limited. We examined the association between graft rejection and vaccination. DESIGN: Matched case-control METHODS: We used electronic health records to identify corneal transplant recipients between January 2008 and August 2022 at Kaiser Permanente Southern California. Cases were transplant recipients who experienced a graft rejection (outcome) during the study period. Randomly selected controls who did not experience a corneal graft rejection at their matched cases' index date (rejection date) were matched in a 3:1 ratio to cases. For controls, index date was determined by adding the number of days between transplant and graft rejection of their matched case to the control's transplant date. RESULTS: The study included 601 cases and 1803 matched controls (mean age 66 years [s.d. 17.0], 52% female, 47% non-Hispanic white). Twenty-three% of cases and 22% of controls received ≥1 vaccinations within 12 weeks prior to the index date. The adjusted odds ratio (aOR) for vaccination in the 12 weeks prior to index date, comparing cases to controls was 1.17 (95% CI: 0.91, 1.50]). The aOR was 1.09 (0.84, 1.43) for 1 vaccination, 1.53 (0.90, 2.61) for 2 vaccinations, and 1.79 (0.55, 5.57) for ≥3 vaccinations. The aOR was 1.60 (0.81, 3.14) for mRNA vaccines, and 1.19 (0.80, 1.78) for adjuvanted/high dose vaccines. CONCLUSIONS: We found no evidence to suggest an association between vaccination and graft rejection. Our findings provide support for the completion of recommended vaccinations for corneal transplant recipients, without significantly increasing the risk of graft rejection.

Human MPox (Monkeypox) Virus Membranous Keratoconjunctivitis With Transient Corneal Hypoesthesia and Late Symblepharon Formation: A Novel Case and Clinical Implications.

PURPOSE: The aim of this study was to describe a case of corneal involvement as an early manifestation of ocular disease in the 2022 human mpox (monkeypox) virus outbreak. METHODS: This is a single case report with longitudinal care. RESULTS: A 47-year-old immunocompetent man presented with viral conjunctivitis before development of skin lesions or systemic symptoms. Subsequently, he developed membranous keratoconjunctivitis and a corneal epithelial defect. Orthopoxvirus-positive polymerase chain reaction test from his ocular surface was positive. The epithelial defect did not heal with conservative treatment but was successfully treated with amniotic membrane transplantation over 8 days. Reduced corneal sensation was noted after epithelial healing, and polymerase chain reaction from the ocular surface remained positive at 17 days from symptom onset, with slowly recovering conjunctivitis at 21 days. Continued membrane formation required repeated removal but significantly improved with topical corticosteroid treatment after epithelial healing by 29 days of symptom onset. Corneal sensation normalized by 87 days from symptom onset at which time symblepharon were noted but PCR testing from the ocular surface was negative. CONCLUSIONS: Early corneal involvement of human monkeypox virus is possible. Transient corneal hypoesthesia may be due to acute inflammation. Chronic inflammatory changes can result in symblepharon. These findings have potential implications in patient care and corneal donation.

Cyclodialysis Cleft After Secondary Intraocular Lens Placement With Yamane Technique.

PURPOSE: The purpose of this study was to report a rare case of cyclodialysis cleft after secondary intraocular lens (IOL) placement using the Yamane flanged intrascleral haptic fixation technique. METHODS: This study is an observational case report. RESULTS: A 74-year-old man with an ocular history of spontaneously dislocated IOL and subsequent anterior chamber IOL (ACIOL) placement presented with monocular diplopia secondary to ACIOL subluxation. The patient underwent explantation of the subluxed ACIOL and placement of a scleral-fixated IOL using the Yamane technique. The postoperative course was complicated by persistent hypotony, prompting ultrasound biomicroscopy, which revealed a cyclodialysis cleft adjacent to one of the externalized IOL haptics. The haptic was discovered in the involved supraciliary space while performing direct cyclopexy. The cyclodialysis cleft closed with return to physiologic intraocular pressure. CONCLUSIONS: Cyclodialysis cleft formation is a possible complication of scleral IOL fixation and should be suspected in cases of prolonged postoperative hypotony. Extended longitudinal tracking of the needle and haptic through the supraciliary space may be one mechanism for cyclodialysis cleft formation in the Yamane technique.

Anterior Uveitis following COVID Vaccination: A Summary of Cases from Global Reporting Systems.

PURPOSE: COVID-19 vaccines are currently undergoing long-term safety monitoring, including for ocular side effects. Uveitis following vaccination has been described previously with other vaccines and warrants evaluation for COVID-19 vaccines, especially given their widespread use. CASE REPORTS: We present two cases of patients who developed anterior uveitis following the Moderna COVID-19 vaccine, as reported to the National Registry for Drug-Induced Ocular Side Effects. We also summarize reports of anterior uveitis following COVID-19 vaccination as reported to the World Health Organization global database of individual case safety reports. CONCLUSIONS: Based on the temporal pattern of ocular inflammation following vaccine delivery in these cases, an association may be present between uveitis and COVID-19 vaccination. Further investigation to explore this association is warranted to guide patient care.

Early Complications With Preloaded Descemet Membrane Endothelial Keratoplasty Are Not Dependent on Optisol-GS Washout or Trypan Blue Restaining.

PURPOSE: To describe the intraoperative and early postoperative complications using preloaded Descemet membrane endothelial keratoplasty (DMEK) grafts with intraocular injection of the graft in Optisol-GS and omission of trypan blue restaining. METHODS: This is a retrospective case series of 132 consecutive eyes with Fuchs endothelial dystrophy or endothelial failure who underwent DMEK using preloaded donor tissue prepared as previously described. The graft was not restained with trypan blue by the surgeon, and Optisol-GS was injected with the graft into the eye instead of being rinsed from the injector. Early postoperative complications (0-8 wk) including intraoperative fibrin formation, intraocular inflammation, elevated intraocular pressure, partial graft detachment requiring rebubble, and early graft failure were recorded. RESULTS: No eyes developed intraoperative fibrin formation or postoperative inflammation (such as toxic anterior segment syndrome) or elevated intraocular pressure. For eyes with Fuchs corneal dystrophy, our rebubble rate was 21% (22/106 eyes). Early graft failure was noted in 2% (3/132 eyes), which is similar to previous reports. CONCLUSIONS: Our results suggest that injection of Optisol-GS into the anterior chamber during DMEK graft injection does not lead to increases in intraoperative or early postoperative complications. Trypan blue restaining is not necessary for intraoperative visualization. This simplification can reduce graft manipulation and save time and resources for this procedure.

Application of Corneal Optical Coherence Tomography Angiography for Assessment of Vessel Depth in Corneal Neovascularization.

PURPOSE: To map and measure the depths of corneal neovascularization (NV) using 3-dimensional optical coherence tomography angiography (OCTA) at 2 different wavelengths. METHODS: Corneal NV of varying severity, distribution, and underlying etiology was examined. Average NV depth and vessel density were measured using 840-nm spectral-domain OCTA and 1050-nm swept-source OCTA. The OCTA results were compared with clinical slit-lamp estimation of NV depth. RESULTS: Twelve eyes with corneal NV from 12 patients were imaged with OCTA. Clinically "superficial," "midstromal," and "deep" cases had an average vessel depth of 23%, 39%, and 66% on 1050-nm OCTA, respectively. Average vessel depth on OCTA followed a statistically significant ordinal trend according to the clinical classification of vessel depth (Jonckheere-Terpstra test, P < 0.001). In 8 cases where both 840-nm OCTA and 1050-nm OCTA were acquired, there was excellent agreement in the mean vessel depth between the 2 systems (concordance correlation coefficient = 0.94, P < 0.001). The average vessel density measured by 840-nm OCTA was higher (average 1.6-fold) than that measured by 1050-nm OCTA. CONCLUSIONS: Corneal OCTA was able to map corneal NV in 3 dimensions and measure vessel depth and density. The depth of corneal NV varied between different pathologies in a manner consistent with previous pathologic studies. The measured vessel density appeared to be affected by the interscan time, which affects blood flow velocity sensitivity, and the wavelength, which affects the ability to penetrate through opacity. These findings suggest possible clinical applications of OCTA for the diagnosis of corneal pathology and quantitative monitoring of therapeutic response in patients with corneal NV.

Evidence for contamination with C. trachomatis in the household environment of children with active Trachoma: A cross-sectional study in Kongwa, Tanzania.

BACKGROUND: Trachoma, a conjunctivitis caused by repeated infections with Chlamydia trachomatis, remains a significant cause of blindness worldwide. While mass treatments with azithromycin decreases disease and infection, re-emergence occurs, indicating that elimination may require other sustainable interventions. Environmental changes largely focus on facial hygiene and latrines, but further work to identify other possible transmission targets are needed. We sought to determine, in a cross-sectional survey of households of children with active trachoma, if we could detect the presence of Chlamydia trachomatis on household objects and on family members based on sleeping and caretaking patterns. METHODS: In five villages in Kongwa, Tanzania, children

Ability of novice clinicians to interpret high-resolution optical coherence tomography for ocular surface lesions.

OBJECTIVE: To assess the ability of novice clinicians to use a commercially available high-resolution anterior segment optical coherence tomography (HR-OCT) device to diagnose various lesions of the ocular surface and cornea. METHODS: Cross-sectional study. Twenty-six black-and-white HR-OCT images were projected, and clinicians were asked to determine whether the lesions represented ocular surface squamous neoplasia (OSSN) or another ocular surface pathology. A 20-minute instructional lecture was given on HR-OCT interpretation, and the same 26 images were shown. The clinicians were asked to repeat their assessment of the lesions. Thirty-four novice clinicians at the Bascom Palmer Eye Institute, Miami, FL, participated. A commercially available device (RTVue, Optovue, Fremont, Calif.) was specifically chosen for this study. RESULTS: The mean frequency of correct identification of the 26 lesions was 70% (standard deviation [SD] 15%) before instruction; after a short lecture, the frequency of correct identification improved to 84% (SD 9%, p = 0.002). Novice clinicians were more accurate in correctly determining that a lesion was not an OSSN (ruling it out as a diagnosis) than in determining that a lesion was an OSSN (p = 0.001). Some lesions (both OSSN and not OSSN), however, were more difficult to interpret than others. CONCLUSION: This study demonstrated that all levels of novice clinicians can quickly improve diagnostic accuracy with a commercially available HR-OCT after a short training session.

Role of high resolution optical coherence tomography in diagnosing ocular surface squamous neoplasia with coexisting ocular surface diseases.

PURPOSE: Coexistence of an ocular surface disease can mask the typical features of ocular surface squamous neoplasia (OSSN). The purpose of this study was to evaluate high resolution optical coherence tomography (HR-OCT) as an adjunct in the detection and differentiation of OSSN within coexisting ocular surface pathologies. METHODS: Retrospective study of 16 patients with ocular surface disease and lesions suspicious for OSSN that were evaluated with HR-OCT. HR-OCT images of the lesions were taken to look for evidence of OSSN. Biopsies were performed in all cases, and the HR-OCT findings were compared to the histological results. RESULTS: Of the 16 patients with OSSN and a coexisting ocular surface disease, 12 were found to have OSSN by HR-OCT and all were subsequently confirmed by biopsy. Two patients had OSSN with rosacea, one with pingueculum, two within pterygia, one with Salzmann' nodular degeneration, six with limbal stem cell deficiency (LSCD)/scarring. In all 12 cases HR-OCT images revealed classical findings of hyper-reflective, thickened epithelium and an abrupt transition from normal to abnormal epithelium. OSSN was ruled out by HR-OCT in four cases (2 Salzmann's, 1 mucous membrane pemphigoid, and 1 LSCD). Negative findings were confirmed by biopsy. HR-OCT was used to follow resolution of the OSSN in positive cases, and it detected recurrence in 1 case. CONCLUSIONS: While histopathology is the gold standard in the diagnosis of OSSN, HR-OCT can be used to noninvasively detect the presence of OSSN in patients with coexisting ocular conditions.

Perioperative antibiotics for prevention of acute endophthalmitis after cataract surgery.

BACKGROUND: Endophthalmitis is a severe inflammation of the anterior or posterior (or both) chambers of the eye that may be sterile or associated with infection. It is a potentially vision-threatening complication of cataract surgery. Prophylactic measures for endophthalmitis are targeted against various sources of infection. OBJECTIVES: To evaluate the effects of perioperative antibiotic prophylaxis for endophthalmitis following cataract surgery compared with no prophylaxis or other form of prophylaxis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 12), Ovid MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to December 2016), Embase (January 1980 to December 2016), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to December 2016),the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 6 December 2016. We also searched for additional studies that cited any included trials using the Science Citation Index. SELECTION CRITERIA: We included randomized controlled trials that enrolled adults undergoing cataract surgery (any method and incision type) for lens opacities due to any origin. We included trials that evaluated preoperative antibiotics, intraoperative (intracameral, subconjunctival or systemic), or postoperative antibiotic prophylaxis for acute endophthalmitis. We excluded studies that evaluated antiseptic preoperative preparations using agents such as povidone iodine or antibiotics for treating acute endophthalmitis after cataract surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed abstracts and full-text articles for eligibility, assessed the risk of bias for each included study, and abstracted data. MAIN RESULTS: Five studies met the inclusion criteria for this review, including 101,005 adults and 132 endophthalmitis cases. While the sample size was very large, the heterogeneity of the study designs and modes of antibiotic delivery made it impossible to conduct a formal meta-analysis. Interventions investigated included the utility of adding vancomycin and gentamycin to the irrigating solution compared with standard balanced saline solution irrigation alone, use of intracameral cefuroxime with or without topical levofloxacin perioperatively, periocular penicillin injections and topical chloramphenicol-sulfadimidine drops compared with topical antibiotics alone, and mode of antibiotic delivery (subconjunctival versus retrobulbar injections; fixed versus separate instillation of gatifloxacin and prednisolone). The risk of bias among studies was low to unclear due to information not being reported. We identified one ongoing study.Two studies compared any antibiotic with no antibiotic. One study, which compared irrigation with antibiotics in balanced salt solution (BSS) versus BSS alone, was not sufficiently powered to detect differences in endophthalmitis between groups (very low-certainty evidence). One study found reduced risk of endophthalmitis when combining intracameral cefuroxime and topical levofloxacin (risk ratio (RR) 0.14, 95% confidence interval (CI) 0.03 to 0.63; 8106 participants; high-certainty evidence) or using intracameral cefuroxime alone (RR 0.21, CI 0.06 to 0.74; 8110 participants; high-certainty evidence) compared with placebo, and an uncertain effect when using topical levofloxacin alone compared with placebo (RR 0.72, CI 0.32 to 1.61; 8103 participants; moderate-certainty evidence).Two studies found reduced risk of endophthalmitis when combining antibiotic injections during surgery and topical antibiotics compared with topical antibiotics alone (risk ratio (RR) 0.33, 95% confidence interval (CI) 0.12 to 0.92 (periocular penicillin and topical chloramphenicol-sulfadimidine; 6618 participants; moderate-certainty evidence); and RR 0.20, 95% CI 0.04 to 0.91 (intracameral cefuroxime and topical levofloxacin; 8101 participants; high-certainty evidence)).One study, which compared fixed versus separate instillation of gatifloxacin and prednisolone, was not sufficiently powered to detect differences in endophthalmitis between groups (very low-certainty evidence). Another study found no evidence of a difference in endophthalmitis when comparing subconjunctival versus retrobulbar antibiotic injections (RR 0.85, 95% CI 0.55 to 1.32; 77,015 participants; moderate-certainty evidence).Two studies reported any visual acuity outcome; one study, which compared fixed versus separate instillation of gatifloxacin and prednisolone, reported only that mean visual acuity was the same for both groups at 20 days postoperation. In the other study, the difference in the proportion of eyes with final visual acuity greater than 20/40 following endophthalmitis between groups receiving intracameral cefuroxime with or without topical levofloxacin compared with no intracameral cefuroxime was uncertain (RR 0.69, 95% CI 0.22 to 2.11; 29 participants; moderate-certainty evidence).Only one study reported adverse events (1 of 129 eyes had pupillary membrane in front of the intraocular lens and 8 eyes showed posterior capsule opacity). No study reported outcomes related to quality of life or economic outcomes. AUTHORS' CONCLUSIONS: Multiple measures for preventing endophthalmitis following cataract surgery have been studied. High-certainty evidence shows that injection with cefuroxime with or without topical levofloxacin lowers the chance of endophthalmitis after surgery, and there is moderate-certainty evidence to suggest that using antibiotic eye drops in addition to antibiotic injection probably lowers the chance of endophthalmitis compared with using injections or eye drops alone. Clinical trials with rare outcomes require very large sample sizes and are quite costly to conduct; thus, it is unlikely that many additional clinical trials will be conducted to evaluate currently available prophylaxis. Practitioners should rely on current evidence to make informed decisions regarding prophylaxis choices.

Surgical versus Medical Treatment of Ocular Surface Squamous Neoplasia: A Cost Comparison.

PURPOSE: The objective of this study was to compare the cost associated with surgical versus interferon-alpha 2b (IFNα2b) treatment for ocular surface squamous neoplasia (OSSN). DESIGN: A matched, case-control study. PARTICIPANTS: A total of 98 patients with OSSN, 49 of whom were treated surgically and 49 of whom were treated medically. METHODS: Patients with OSSN treated with IFNα2b were matched to patients treated with surgery on the basis of age and date of treatment initiation. Financial cost to the patient was calculated using 2 different methods (hospital billing and Medicare allowable charges) and compared between the 2 groups. These fees included physician fees (clinic, pathology, anesthesia, and surgery), facility fees (clinic, pathology, and operating room), and medication costs. Time invested by patients was calculated in terms of number of visits to the hospital and compared between the 2 groups. Parking costs, transportation, caregiver wages, and lost wages were not considered in our analysis. MAIN OUTCOME MEASURES: Number of clinic visits and cost of therapy as represented by both hospital charges and Medicare allowable charges. RESULTS: When considering cost in terms of time, the medical group had an average of 2 more visits over 1 year compared with the surgical group. Cost as represented by hospital charges was higher in the surgical group (mean, $17 598; standard deviation [SD], $7624) when compared with the IFNα2b group (mean, $4986; SD, $2040). However, cost between the 2 groups was comparable when calculated on the basis of Medicare allowable charges (surgical group: mean, $3528; SD, $1610; medical group: mean, $2831; SD, $1082; P = 1.00). The highest cost in the surgical group was the excisional biopsy (hospital billing $17 598; Medicare allowable $3528), and the highest cost in the medical group was interferon ($1172 for drops, average 8.0 bottles; $370 for injections, average 5.4 injections). CONCLUSIONS: Our data in this group of patients previously demonstrated equal efficacy of surgical versus medical treatment. In this article, we consider costs of therapy and found that medical treatment involved two more office visits, whereas surgical treatment could be more or equally costly depending on insurance coverage.

Human Papilloma Virus Infection Does Not Predict Response to Interferon Therapy in Ocular Surface Squamous Neoplasia.

PURPOSE: To identify the frequency of human papilloma virus (HPV) in ocular surface squamous neoplasia (OSSN) and to evaluate differences in clinical features and treatment response of tumors with positive versus negative HPV results. DESIGN: Retrospective case series. PARTICIPANTS: Twenty-seven patients with OSSN. METHODS: Ocular surface squamous neoplasia specimens were analyzed for the presence of HPV. Clinical features and response to interferon were determined retrospectively and linked to the presence (versus absence) of HPV. MAIN OUTCOME MEASURES: Clinical characteristics of OSSN by HPV status. RESULTS: Twenty-one of 27 tumors (78%) demonstrated positive HPV results. The HPV genotypes identified included HPV-16 in 10 tumors (48%), HPV-31 in 5 tumors, HPV-33 in 1 tumor, HPV-35 in 2 tumors, HPV-51 in 2 tumors, and a novel HPV in 3 tumors (total of 23 tumors because 1 tumor had 3 identified genotypes). Tumors found in the superior limbus were more likely to show positive HPV results (48% vs. 0%; P=0.06, Fisher exact test). Tumors with positive HPV-16 results were larger (68 vs. 34 mm2; P=0.08, Mann-Whitney U test) and were more likely to have papillomatous morphologic features (50% vs. 12%; P=0.07, Fisher exact test) compared with tumors showing negative results for HPV-16. Human papilloma virus status was not found to be associated with response to interferon therapy (P=1.0, Fisher exact test). Metrics found to be associated with a nonfavorable response to interferon were male gender and tumors located in the superior conjunctivae. CONCLUSIONS: The presence of HPV in OSSN seems to be more common in lesions located in the nonexposed, superior limbus. Human papilloma virus presence does not seem to be required for a favorable response to interferon therapy.

High-Resolution Optical Coherence Tomography as an Adjunctive Tool in the Diagnosis of Corneal and Conjunctival Pathology.

PURPOSE: To evaluate the use of a commercially available, high-resolution, spectral-domain optical coherence tomography (HR-OCT) device in the diagnosis of corneal and conjunctival pathologies, with a focus on malignant lesions. METHODS: Eighty-two eyes of 71 patients were enrolled in this prospective case series, including 10 normal eyes, 21 with ocular surface squamous neoplasia (OSSN), 24 with a pterygium or pingueculum, 3 with lymphoma, 18 with pigmented conjunctival lesions (nevus, flat melanosis, or melanoma), and 6 with Salzmann nodular degeneration. Subjects were imaged using photography and HR-OCT (RTVue, Optovue, Fremont, CA). When clinically indicated, surgery was performed and histopathologic specimens were correlated with OCT images. RESULTS: HR-OCT was useful in differentiating among various lesions based on optical signs. Specifically, in OSSN, HR-OCT findings included epithelial thickening and hyper-reflectivity, whereas pterygia and pinguecula showed a subepithelial mass under thinner epithelium. In lymphoma, a hypo-reflective, homogenous subepithelial mass was observed. Differentiating between pigmented lesions with HR-OCT was more difficult, but certain characteristics could be identified. Eyes with nevi and melanoma both displayed intensely hyper-reflective basal epithelial layers and discrete subepithelial lesions, but could be differentiated by the presence of cysts in nevi and intense shadowing of sublesional tissue in most melanomas. CONCLUSION: We found that a commercially available HR-OCT was a useful noninvasive adjunctive tool in the diagnosis of ocular surface lesions.

Anti-vascular endothelial growth factor for macular oedema secondary to central retinal vein occlusion.

BACKGROUND: Central retinal vein occlusion (CRVO) is a relatively common retinal vascular disorder in which macular oedema may develop, with a consequent reduction in visual acuity. Until recently there has been no treatment of proven benefit, but growing evidence supports the use of anti-vascular endothelial growth factor (anti-VEGF) agents. OBJECTIVES: To investigate the effectiveness and safety of anti-VEGF therapies for the treatment of macular oedema secondary to CRVO. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 10), Ovid MEDLINE (January 1950 to October 2013), EMBASE (January 1980 to October 2013), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to October 2013), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to October 2013), OpenGrey, OpenSIGLE (January 1950 to October 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and Web of Science Conference Proceedings Citation Index-Science (CPCI-S). There were no language or date restrictions in the electronic search for trials. The electronic databases and clinical trials registers were last searched on 29th October 2013. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) that compared intravitreal anti-VEGF agents of any dose or duration to sham injection or no treatment. We focused on studies that included individuals of any age or gender and a minimum of six months follow-up. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. The primary outcome was the proportion of participants with a gain in best-corrected visual acuity (BCVA) from baseline of greater than or equal to 15 letters (3 lines) on the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. Secondary outcomes included the proportion of participants with a loss of 15 letters or more of BCVA, the mean change from baseline BCVA, the mean change in central retinal thickness (CRT), the number and type of complications or adverse outcomes, and the number of additional interventions administered. Where available, we also presented quality of life and economic data. MAIN RESULTS: We found six RCTs that met the inclusion criteria after independent and duplicate review of the search results. These RCTs included 937 participants and compared outcomes at six months to sham injection for four anti-VEGF agents: aflibercept (VEGF Trap-Eye, Eylea), bevacizumab (Avastin), pegaptanib sodium (Macugen) and ranibizumab (Lucentis). Three trials were conducted in Norway, Sweden and the USA, and three trials were multicentre, one including centres in the USA, Canada, India, Israel, Argentina and Columbia, a second including centres in the USA, Australia, France, Germany, Israel, and Spain, and a third including centres in Austria, France, Germany, Hungary, Italy, Latvia, Australia, Japan, Singapore and South Korea. We performed meta-analysis on three key visual outcomes, using data from up to six trials. High-quality evidence from six trials revealed that participants receiving intravitreal anti-VEGF treatment were 2.71 times more likely to gain at least 15 letters of visual acuity at six months compared to participants treated with sham injections (risk ratio (RR) 2.71; 95% confidence intervals (CI) 2.10 to 3.49). High-quality evidence from five trials suggested anti-VEGF treatment was associated with an 80% lower risk of losing at least 15 letters of visual acuity at six months compared to sham injection (RR 0.20; 95% CI 0.12 to 0.34). Moderate-quality evidence from three trials (481 participants) revealed that the mean reduction from baseline to six months in central retinal thickness was 267.4 µm (95% CI 211.4 µm to 323.4 µm) greater in participants treated with anti-VEGF than in participants treated with sham. The meta-analyses demonstrate that treatment with anti-VEGF is associated with a clinically meaningful gain in vision at six months. One trial demonstrated sustained benefit at 12 months compared to sham. No significant ocular or systemic safety concerns were identified in this time period. AUTHORS' CONCLUSIONS: Compared to no treatment, repeated intravitreal injection of anti-VEGF agents in eyes with CRVO macular oedema improved visual outcomes at six months. All agents were relatively well tolerated with a low incidence of adverse effects in the short term. Future trials should address the relative efficacy and safety of the anti-VEGF agents and other treatments, including intravitreal corticosteroids, for longer-term outcomes.

Surgical versus medical treatment of ocular surface squamous neoplasia: a comparison of recurrences and complications.

PURPOSE: Treatment for ocular surface squamous neoplasia (OSSN) has historically been surgery, but nonsurgical interventions are increasingly used. Treatment with interferon is efficacious, but evidence is needed regarding recurrence and complication rates in comparison with surgery. The objective of this study is to compare the recurrence and complication rates of surgical treatment and interferon treatment for OSSN. DESIGN: A matched, case-control study. PARTICIPANTS: Ninety-eight patients with OSSN, 49 of whom were treated with interferon (IFN) α2b therapy and 49 of whom were treated with surgical intervention. METHODS: Patients with OSSN were treated with surgery versus IFNα2b therapy, either in topical or injection form. Median follow-up after lesion resolution was 21 months (range, 0-173 months) for the IFNα2b group and 24 months (range, 0.9-108 months) for the surgery group. MAIN OUTCOME MEASURES: The primary outcome measure for the study was the rate of recurrence of OSSN in each of the treatment groups. Recurrence rates were evaluated using Kaplan-Meier survival analysis. RESULTS: Mean patient age and sex were similar between the groups. There was a trend toward higher clinical American Joint Committee on Cancer tumor grade in the IFNα2b group. Despite this, the number of recurrences was equal at 3 per group. The 1-year recurrence rate was 5% in the surgery group versus 3% in the IFNα2b group (P = 0.80). There was no statistically significant difference in the recurrence rate between the surgically and medically treated groups. Nonlimbal location was a risk factor for recurrence (hazard ratio, 8.96) in the entire study population. In patients who were treated successfully, the side effects of the 2 treatments were similar, with mild discomfort seen in the majority of patients in both groups. There was no limbal stem cell deficiency, symblepharon, or diplopia noted in either group. Two patients were excluded from the IFNα2b group because of intolerance to the medication. CONCLUSIONS: No difference in the recurrence rate of OSSN was found between surgical versus IFNα2b therapy.