Corneal collagen cross-linking for treating keratoconus.

BACKGROUND: Keratoconus is a condition of the eye that affects approximately 1 in 2000 people. The disease leads to a gradual increase in corneal curvature and decrease in visual acuity with consequent impact on quality of life. Collagen cross-linking (CXL) with ultraviolet A (UVA) light and riboflavin (vitamin B2) is a relatively new treatment that has been reported to slow or halt the progression of the disease in its early stages. OBJECTIVES: The objective of this review was to assess whether there is evidence that CXL is an effective and safe treatment for halting the progression of keratoconus compared to no treatment. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2014), EMBASE (January 1980 to August 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to August 2014), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to August 2014), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organisation 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 28 August 2014. SELECTION CRITERIA: We included randomised controlled trials (RCTs) where CXL with UVA light and riboflavin was used to treat people with keratoconus and was compared to no treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results, assessed trial quality, and extracted data using standard methodological procedures expected by Cochrane. Our primary outcomes were two indicators of progression at 12 months: increase in maximum keratometry of 1.5 dioptres (D) or more and deterioration in uncorrected visual acuity of more than 0.2 logMAR. MAIN RESULTS: We included three RCTs conducted in Australia, the United Kingdom, and the United States that enrolled a total of 225 eyes and analysed 219 eyes. The total number of people enrolled was not clear in two of the studies. Only adults were enrolled into these studies. Out of the eyes analysed, 119 had CXL (all using the epithelium-off technique) and 100 served as controls. One of these studies only reported comparative data on review outcomes. All three studies were at high risk for performance bias (lack of masking), detection bias (only one trial attempted to mask outcome assessment), and attrition bias (incomplete follow-up). It was not possible to pool data due to differences in measuring and reporting outcomes. We identified a further three unpublished trials that potentially had enrolled a total of 195 participants.There was limited evidence on the risk of progression. Analysis of the first few participants followed up to one year in one study suggested that eyes given CXL were less likely to have an increase in maximum keratometry of 1.5 D or more at 12 months compared to eyes given no treatment, but the confidence intervals (CI) were wide and compatible with no effect or more progression in the CXL group (risk ratio (RR) 0.12, 95% CI 0.01 to 2.00, 19 eyes). The same study reported the number of eyes with an increase of 2 D or more at 36 months in the whole cohort with a RR of 0.03 favouring CXL (95% CI 0.00 to 0.43, 94 eyes). Another study reported "progression" at 18 months using a different definition; people receiving CXL were less likely to progress, but again the effect was uncertain (RR 0.14, 95% CI 0.01 to 2.61, 44 eyes). We judged this to be very low-quality evidence due to the risk of bias of included studies, imprecision, indirectness and publication bias but noted that the size of the potential effect was large.On average, treated eyes had a less steep cornea (approximately 2 D less steep) (mean difference (MD) -1.92, 95% CI -2.54 to -1.30, 94 eyes, 1 RCT, very low-quality evidence) and better uncorrected visual acuity (approximately 2 lines or 10 letters better) (MD -0.20, 95% CI -0.31 to -0.09, 94 eyes, 1 RCT, very low-quality evidence) at 12 months. None of the studies reported loss of 0.2 logMAR acuity. The data on corneal thickness were inconsistent. There were no data available on quality of life or costs. Adverse effects were not uncommon but mostly transient and of low clinical significance. In one trial, 3 out of 12 participants treated with CXL had an adverse effect including corneal oedema, anterior chamber inflammation, and recurrent corneal erosions. In one trial at 3 years 3 out of 50 participants experienced adverse events including mild diffuse corneal oedema and paracentral infiltrate, peripheral corneal vascularisation, and subepithelial infiltrates and anterior chamber inflammation. No adverse effects were reported in the control groups. AUTHORS' CONCLUSIONS: The evidence for the use of CXL in the management of keratoconus is limited due the lack of properly conducted RCTs.

Conservative resection and adjuvant plaque brachytherapy for early-stage conjunctival melanoma.

BACKGROUND: To describe the outcome of patients treated by conservative surgical excision followed by adjuvant plaque brachytherapy for early-stage primary or recurrent conjunctival melanoma. DESIGN: Retrospective, non-comparative, interventional case series. PARTICIPANTS: We reviewed 19 eyes in 19 consecutive patients presenting with biopsy proven conjunctival melanoma with pathologic stage pT1c or less. METHODS: Patients with primary or recurrent early-stage conjunctival melanoma were identified and treated using a conservative resection technique (tractional micro-dissection) involving avoidance of deep dissection and modest lateral clearance followed by adjuvant plaque brachytherapy. MAIN OUTCOME MEASURE: Local recurrence and ocular complications. RESULTS: Mean age was 55.2 years and male : female (8:11). Mean follow up was 43.1 months (range 30.1-54.3 months). All patients were treated by conservative resection followed by adjuvant Iodine-125 plaque brachytherapy. The treatment dose was 100 Gy to a depth of 1.5-3.0 mm. OUTCOMES: median visual acuity and intraocular pressure were unchanged after surgery. Six patients experienced corneal ulceration in the immediate postoperative period. No patients experienced recurrence at the treatment site or metastases. Three patients experienced new lesions distant from the treatment site. CONCLUSIONS: Conservative resection and adjuvant plaque brachytherapy is an effective and well-tolerated modality for the management of patients with early-stage conjunctival melanoma.

Primary trabeculectomy with mitomycin C: safety and efficacy at 2 years.

PURPOSE: To examine the rates of intermediate-term intraocular pressure (IOP) control after trabeculectomy with adjunctive mitomycin C (MMC) and assess for associated complications. METHODS: Medical records of patients undergoing primary trabeculectomy with MMC at Concord Repatriation Hospital, Sydney between January 1997 and December 2005 were reviewed. All eyes with a minimum of 2-year follow up were included. Follow-up data were collected in a standardized form on postoperative IOP, bleb-related and other complications. Success was measured as IOP ≤ 18 mmHg and ≥ 6 mmHg (criteria 1) with (qualified success) or without (absolute success) the use of glaucoma medications. A secondary outcome measure was an IOP reduction of greater than 20% from baseline (criteria 2). Eyes with preoperative IOP of 18 mmHg or less were included, but also analysed separately to those eyes with preoperative IOP above 18 mmHg. RESULTS: Sixty eyes from 42 patients were included in the study, with 3-year follow up on 48 eyes. Mean preoperative IOP was 25.3 mmHg (range 8-45) and mean postoperative IOP was 14.0 mmHg at 1- and 2-year follow up, and 14.7 mmHg at 3 years (ranges: 3-31, 4-30 and 8-45 mmHg respectively). Cumulative success for criteria 1 was 85.0% at 2 years and 83.3% at 3 years, and for criteria 2 it was 80.0% and 79.2%, respectively. The number of eyes on glaucoma medications was reduced from 51 preoperatively to 30 at 3 years. Complications were infrequent. There was one eye with a shallow anterior chamber beyond the immediate postoperative period. One eye required cataract surgery at 1-year follow up. Subgroup analysis was performed using the first operated eye only, and results did not differ significantly from overall results. CONCLUSION: MMC-augmented trabeculectomy can significantly reduce IOP in the short and intermediate term, with a favourable safety profile.

Optic atrophy in children: Current causes and diagnostic approach.

BACKGROUND/AIMS: Optic atrophy is one of the leading causes of sight impairment in children. It frequently poses a diagnostic challenge, as it can be caused by many ocular and systemic conditions. We aimed to determine the current causes of optic atrophy at our centre and to describe the use of investigations, including molecular genetic testing. METHODS: We reviewed the medical records of children with optic atrophy seen at Moorfields Eye Hospital between 2010 and 2015. We recorded demographic data, reason for referral, history, investigations and diagnosis. RESULTS: We studied 143 cases aged below 16 years. A cause could be identified in all cases. Taking a full history was the most important part of the diagnostic workup, identifying a cause in 96 (67%) children. A developmental disorder of the brain and/or optic nerve, sometimes with retinal involvement, was the commonest cause (n = 33, 23%), followed by inheritable optic neuropathies (n = 27, 19%). Other causes included perinatal insults (n = 18, 13%), post-infectious or post-inflammatory conditions (n = 18, 13%), accidental or abusive trauma (n = 14, 10%) and inheritable retinal dystrophies (n = 13, 9%). Rare conditions included neurodegenerative disorders (n = 7, 5%), skeletal developmental disorders such as rickets (n = 4, 3%), tumours (n = 4, 3%), ischaemic events including large optic nerve head drusen (n = 4, 3%) and toxic events/metabolic conditions (n = 1, 0.7%). CONCLUSION: In this series, an underlying cause could be identified in all cases. Taking a comprehensive antenatal, perinatal, postnatal and family history will indicate a probable diagnosis in two-thirds of children, and targeted ancillary tests may identify the cause in most remaining cases.

Management of giant fornix syndrome with irrigation with povidone-iodine.

Giant fornix syndrome (GFS) was first described as a cause for a relapsing mucopurulent conjunctivitis. Predominantly elderly patients have enlarged superior fornices from superior aponeurosis dehiscence that permits the accumulation of protein coagulum that is colonised by bacteria. Established treatment includes the use of intensive topical antibiotic and corticosteroid. We describe a case of a 98-year-old woman with GFS who did not respond to several weeks of intensive (two hourly) treatment with topical prednisolone 1% drops and chloramphenicol. Subsequent additional regular sweeping of the fornices with cotton buds and topical medication did not improve her symptoms but which resolved with manual coagulum debridement and application of 10% povidone-iodine. This treatment offers an effective treatment option of GFS cases, which do not respond to intensive topical corticosteroids and chloramphenicol.

Study of fluid ingress through clear corneal incisions following phacoemulsification with or without the use of a hydrogel ocular bandage: a prospective comparative randomised study.

PURPOSE: To assess the use of a hydrogel ocular bandage (HOB) on clear corneal incisions in phacoemulsification cataract surgery and determine whether HOB reduces ocular surface contaminants ingress after routine surgery. METHODS: In this prospective randomized controlled study, thirty eyes of patients undergoing uneventful phacoemulsification were recruited consecutively and randomly assigned to have a HOB applied to the corneal incision at the end of the surgery or not. At the end of the surgery, trypan blue (TRB) was instilled on the ocular surface, aqueous fluid was aspirated from the anterior chamber (AC) and its optical density was measured using ultraviolet spectrophotometry. The corneal incisions were examined postoperatively using anterior segment optical coherence tomography. Main outcome measures were concentration of TRB in the AC, corneal incision architecture, intraocular pressure (IOP) and Seidel test. RESULTS: All incisions were Seidel negative. The mean IOP in the immediate postoperative period was 18.1 ± 5.48 mmHg for the intervention group and 16.9 ± 5.7 mmHg for the control group (p > 0.05). No architectural differences of the incisions between the two groups were noted. The total mean length of the three-step corneal incisions in the two groups was 2261.2 ± 96.92 µm and 2263 ± 119.75 µm, respectively (p > 0.05). No trace of TRB was detected in any of the samples. CONCLUSION: Proper surgical wound construction without the use of a HOB is efficient in preventing the ingress of fluid through the main corneal incision postoperatively.

Management of patients with herpes simplex virus eye disease having cataract surgery in the United Kingdom.

To standardize the management of patients with herpetic eye disease scheduled for cataract surgery, a questionnaire was sent to each fellow of the Royal College of Ophthalmologists registered as a consultant with a subspecialty interest in cornea. Most respondents agreed that disease stability was required before cataract surgery was offered; 62.3% would operate on patients in whom the disease had been quiescent for 3 to 6 months. The decision to prescribe prophylactic antivirals divided the respondents, with 58.8% in favor of starting antiviral treatment. Most respondents (72.46%) did not start topical antiviral treatment. In regard to changing topical steroid use postoperatively, 80.9% would not change their routine regimen. Oral acyclovir was the first line of treatment for 92.5%. The conclusions were that a significant period of inactivity should be considered before cataract surgery is performed in patients with herpes simplex virus eye disease. Oral antiviral prophylaxis is common clinical practice, but no change in routine postoperative steroid use is needed.

Interventions for the treatment of uveitic macular edema: a systematic review and meta-analysis.

BACKGROUND: Uveitic macular edema is the major cause of reduced vision in eyes with uveitis. OBJECTIVES: To assess the effectiveness of interventions in the treatment of uveitic macular edema. SEARCH STRATEGY: Cochrane Central Register of Controlled Trials, Medline, and Embase. There were no language or data restrictions in the search for trials. The databases were last searched on December 1, 2011. Reference lists of included trials were searched. Archives of Ophthalmology, Ophthalmology, Retina, the British Journal of Ophthalmology, and the New England Journal of Medicine were searched for clinical trials and reviews. SELECTION CRITERIA: Participants of any age and sex with any type of uveitic macular edema were included. Early, chronic, refractory, or secondary uveitic macular edema were included. We included trials that compared any interventions of any dose and duration, including comparison with another treatment, sham treatment, or no treatment. DATA COLLECTION AND ANALYSIS: Best-corrected visual acuity and central macular thickness were the primary outcome measures. Secondary outcome data including adverse effects were collected. CONCLUSION: More results from randomized controlled trials with long follow-up periods are needed for interventions for uveitic macular edema to assist in determining the overall long-term benefit of different treatments. The only intervention with sufficiently robust randomized controlled trials for a meta-analysis was acetazolamide, which was shown to be ineffective in improving vision in eyes with uveitic macular edema, and is clinically now rarely used. Interventions showing promise in this disease include dexamethasone implants, immunomodulatory drugs and anti-vascular endothelial growth-factor agents. When macular edema has become refractory after multiple interventions, pars plana vitrectomy could be considered. The disease pathophysiology is uncertain and the course of disease unpredictable. As there are no clear guidelines from the literature, interventions should be tailored to the individual patient.

Use of antivascular endothelial growth factor for diabetic macular edema.

BACKGROUND: Diabetic macular edema (DME) is one of the manifestations of diabetic retinopathy leading to loss of central vision and visual acuity. It manifests itself with swelling around the central part of the retina, the area responsible for sharp vision. Current treatment includes laser therapy and intravitreal steroids with preventative measures including diabetes control. No one treatment has guaranteed control of diabetic macular edema which leads to deteriorating visual acuity, function and quality of life in patients. Vascular endothelial growth factor (VEGF) has been shown to be a critical stimulus in the pathogenesis of macular edema secondary to diabetes.1 Antiangiogenic therapy encompassed treatment with anti-VEGF which inhibits VEGF-driven neovascularization hence macular edema leading to decreased visual acuity. OBJECTIVE: For this review, we evaluated the effectiveness of intravitreal anti-VEGF in treating DME. DATA SOURCES: We identified five trials (n = 525) using electronic databases (Cochrane Central Register of Controlled Trials [Central], Medline((R)), and Excerpta Medica Database [EMBASE((R))]) in October 2008, supplemented by hand searching of reference lists, review articles, and conference abstracts. METHODS: We included all randomized clinical trials (RCTs) evaluating any form of intravitreal anti-VEGF for treating DME. The main outcome factor was change in best-corrected visual acuity and central macular thickness. One author assessed eligibility, methodological quality, and extracted data. Meta analysis was performed when appropriate. RESULTS: We included three trials of adequate methodological quality in our meta-analysis. Patients treated with anti-VEGF showed improvement in visual acuity of -0.17 (95% confidence interval [CI]: -0.23, -0.10) and central macular thickness -84.69 (95% CI: -117.09, -52.30). Patients treated with combined anti-VEGF and intravitreal triamcinolone showed improvement of visual acuity of -0.19 (95% CI: -0.27, -0.11) and central macular thickness mean change being -111.20 (95% CI: -148.13, -74.28). CONCLUSIONS: Anti-VEGF has been associated with an improvement in visual acuity and central macular thickness in the analysis, however trial analysis was of a short duration and further research is needed to determine long-term benefits.

Transitional cell carcinoma of the nasolacrimal sac.

Tumors in the lacrimal sac are rare yet important due to their malignant and potentially lethal outcomes if there is a misdiagnosis or delay in treatment. Epithelial tumors predominate with squamous cell carcinoma. We report a transitional cell carcinoma of the lacrimal sac and management course for the patient.