Cardiometabolic factors and risk of non-arteritic anterior ischemic optic neuropathy: a systematic review and meta-analysis.

PURPOSE: The purpose of this systematic review and meta-analysis of the literature is to evaluate the association between cardiometabolic risk factors (hypertension, diabetes mellitus, hypercholesterolemia/dyslipidemia, HDL cholesterol, LDL cholesterol, lipoprotein(a), and triglycerides) and non-arteritic anterior ischemic optic neuropathy (NAION). METHODS: Pertinent publications were identified through a systematic search in PubMed and EMBASE databases, without language restrictions. The pooled odds ratios (OR) and standardized mean differences (SMD), with their 95% confidence intervals (95% CI) were estimated using random effects (DerSimonian Laird) models, as appropriate. A set of subgroup analyses and meta-regression analysis models were performed. RESULTS: Twenty-one studies (including 1560 patients with NAION and 2292 controls), examining the association between NAION and cardiometabolic risk factors, were eligible for the systematic review and meta-analysis. Hypertension (pooled OR = 1.50; 95% CI: 1.16-1.94), diabetes mellitus (pooled OR = 1.71; 95% CI: 1.33-2.21), and hypercholesterolemia/dyslipidemia (pooled OR = 2.00; 95% CI: 1.53-2.62) were associated with NAION. Among the components of dyslipidemia, higher serum triglycerides were associated with NAION, with a medium effect size (SMD = + 0.58, 95% CI: + 0.12 to + 1.04), whereas synthesis of four studies reporting on HDL and LDL cholesterol did not reveal any significant associations. A significant association between NAION and higher serum lipoprotein(a) levels (pooled OR = 2.88; 95%CI: 1.01-8.21) was also noted. CONCLUSIONS: This systematic review and meta-analysis found that NAION was associated with cardiometabolic factors, suggesting that vascular dysfunction may be implicated in the pathogenesis of the disease. Our findings may alert health care providers to try modifying these risk factors for NAION prevention.

INTERNAL LIMITING MEMBRANE PEELING IN MACULAR HOLE SURGERY; WHY, WHEN, AND HOW?

PURPOSE: To review the current rationale for internal limiting membrane (ILM) peeling in macular hole (MH) surgery and to discuss the evidence base behind why, when, and how surgeons peel the ILM. METHODS: Review of the current literature. RESULTS: Pars plana vitrectomy is an effective treatment for idiopathic MH, and peeling of the ILM has been shown to improve closure rates and to prevent postoperative reopening. However, some authors argue against ILM peeling because it results in a number of changes in retinal structure and function and may not be necessary in all cases. Furthermore, the extent of ILM peeling optimally performed and the most favorable techniques to remove the ILM are uncertain. Several technique variations including ILM flaps, ILM scraping, and foveal sparing ILM peeling have been described as alternatives to conventional peeling in specific clinical scenarios. CONCLUSION: Internal limiting membrane peeling improves MH closure rates but can have several consequences on retinal structure and function. Adjuvants to aid peeling, instrumentation, technique, and experience may all alter the outcome. Hole size and other variables are important in assessing the requirement for peeling and potentially its extent. A variety of evolving alternatives to conventional peeling may improve outcomes and need further study.

Evolution of vitreomacular adhesion to acute vitreofoveal separation with special emphasis on a traction-induced foveal pathology. A prospective study of spectral-domain optical coherence tomography.

PURPOSE: To investigate the evolution of vitreomacular adhesion (VMA) to acute vitreofoveal separation with particular emphasis on cases involving the underlying fovea. METHODS: In this observational case series, of 192 cases in the VMA stage, 51 progressed to acute vitreofoveal separation; this subgroup was divided into those with normal separation (Group I) and those with co-existing macular findings (Group II). All patients were examined using spectral domain-optical coherence tomography (SD-OCT) at regular three-month intervals. We recorded the best-corrected visual acuity (BCVA), the vitreomacular angle of the VMA (nasally and temporally), the horizontal diameter of the VMA, the macular thickness, the integrity of the photoreceptor layer and of the external limiting membrane. The Amsler grid test was used in the intermediate examinations in cases where patients developed symptoms. RESULTS: Out of the 51 cases in the VMA stage, 45 (88.2%) progressed to normal spontaneous vitreofoveal separation, while six (11.8%) developed findings of the fovea, such as macular thinning (two cases), an anomalous foveal contour (two cases), a macular tissue defect (one case) and vitreous separation from only the temporal side of the VMA in one case. Foveal findings were the same during the follow-up period in all but one case in which improvement was noted. Differences in BCVA between baseline measurements, those made immediately after vitreofoveal separation, and those made during final examination were not statistically significant. For the whole sample of our study (51 cases), the mean observation time at the VMA stage was 21.8 ±10.6 months, while the mean follow-up time after vitreofoveal separation was 9.7 ±4.9 months. In cases that developed incidents from the fovea, the mean observation time from the baseline to the last examination before vitreofoveal separation was 16.5 ±11.2 months and the mean follow-up time from the diagnosis of vitreofoveal separation to the final examination was 8.5 ±4.4 months. CONCLUSIONS: VMA, excepting its progression to vitreomacular traction or spontaneous release, in a subset of patients can also cause findings associated with the fovea, concomitantly with vitreofoveal separation. Vitreofoveal separation can induce unilateral anatomic distortion of the fovea accompanied by symptoms, such as metamorphopsia or micropsia.

Effect of macular ischemia on intravitreal ranibizumab treatment for diabetic macular edema.

PURPOSE: To evaluate the impact of macular ischemia on the functional and anatomical outcome after intravitreal injections of ranibizumab for the treatment of diabetic macular edema (DME). PROCEDURES: Participants were 49 patients with diabetes mellitus, divided into two groups based on the presence of ischemia on fluorescein angiography: (i) nonischemic group (n = 32) and (ii) ischemic group (n = 17). All patients were treated with intravitreal ranibizumab and were followed up for 6 months. The main outcome measures were changes in visual acuity (VA) and central foveal thickness (CFT). RESULTS: There was a statistically significant improvement in VA and CFT between baseline and the end of the follow-up in the nonischemic group, while in the ischemic group there was no significant difference in VA but CFT differed significantly at the 6-month follow-up. CONCLUSIONS: Macular ischemia may have a negative impact on functional outcomes 6 months after intravitreal ranibizumab treatment in patients with DME but has no effect on anatomical outcomes.

Diet and cataract: a case-control study.

We conducted a case-control study to assess the association between diet and risk of cataract in Athens, Greece. Totals of 314 cases and 314 frequency-matched controls of both sexes, aged 45-85 years and attending the ophthalmology department of a major teaching hospital in Athens, Greece, were included in the study. All participants were interviewed using a semi-quantitative food-frequency questionnaire, covering the average frequency of consumption of about 120 food items. Analyses were conducted through multiple logistic regression. The analysis was carried out taking cataract as a general outcome (all types of cataract combined) and repeated by the specific type of cataract. We found significant inverse associations of cataract with dietary consumption of fish (OR = 0.69, p < 0.001), vegetables (OR = 0.47, p < 0.001), fruits (OR = 0.53, p < 0.001), and potatoes (OR = 0.76, p = 0.004), while consumption of meat was positively associated with cataract (OR = 1.46, p = 0.001). High intake of total fat (OR = 2.00, p < 0.001) and cholesterol (OR = 1.65, p < 0.001) increased the risk of cataract. There was a protective association between cataract risk and intake of carbohydrates (OR = 0.39, p < 0.001), carotene (OR = 0.56, p < 0.001), vitamins C and E (OR = 0.50, p < 0.001 and OR = 0.50, p < 0.001 respectively). We identified an association between the risk of cataract and several food groups and nutrients. Diets rich in fruits, vegetables, fish, pulses and starchy foods may protect against cataract. In addition, high intake of vitamins C and E and carotene with reduction of intake in total fat and cholesterol may be beneficial. Dietary advice along these lines may provide adequate public health guidelines for the delay of age-related cataract.

Restoration of the photoreceptor layer and improvement of visual acuity in successfully treated optic disc pit maculopathy: a long follow-up study by optical coherence tomography.

PURPOSE: To investigate by optical coherence tomography (OCT) the evolution of the photoreceptor layer and its association with best-corrected visual acuity (BCVA) in optic disc pit (ODP) maculopathy after successful surgical treatment. METHODS: Fourteen eyes of 14 patients were included in this study, and followed up from 36 to 95 months (mean 57.36 ± 18.32 months). The follow-up period started at the time of complete subretinal fluid absorption. Examination was performed by time-domain OCT before and after treatment. Spectral-domain OCT was used after treatment. Parameters assessed were type of elevation, central foveal thickness, time elapsed from onset to treatment, type of treatment, BCVA, and inner segment outer segment (IS/OS) junction line. The IS/OS junction was characterized after treatment as intact, interrupted, or absent (not distinguishable). RESULTS: Significant restoration of the IS/OS junction line was first noticed between 6 and 12 months after fluid absorption (p = 0.02; Wilcoxon signed rank test). Restoration was continuous up to the 24th month of postoperative examination after fluid absorption (p = 0.14; Wilcoxon signed rank test). BCVA was 0.99 ± 0.38 logMar before treatment, 0.81 ± 0.26 logMar (p = 0.011; paired t-test) immediately after fluid absorption and 0.61 ± 0.33 logMar (p = 0.026; one-way ANOVA) 24 months after fluid resolution. BCVA was significantly positively correlated with the integrity of the IS/OS junction line during follow-up (Pearson r = 0.775; p < 0.001). CONCLUSIONS: The IS/OS junction restoration cannot be detected immediately after fluid resolution in the majority of cases. It became evident 6-12 months later and was completed 24 months after fluid absorption. Improvement in BCVA was noticed only during the first 2 years of follow-up. No significant changes were noticed in BCVA or the IS/OS line after 2 years. Among the studied variables, the final photoreceptor layer condition and BCVA immediately after fluid absorption are the main factors predicting final BCVA after successful surgical treatment of ODP maculopathy.

Long-term results of intravitreal ranibizumab, intravitreal ranibizumab with photodynamic therapy, and intravitreal triamcinolone with photodynamic therapy for the treatment of retinal angiomatous proliferation.

PURPOSE: To compare intravitreal ranibizumab, intravitreal ranibizumab plus photodynamic therapy (PDT), and intravitreal triamcinolone plus PDT in retinal angiomatous proliferation, presenting the results of a 3-year follow-up. METHODS: Thirty-seven eyes of 37 patients with retinal angiomatous proliferation were randomized to 1 of the 3 groups. Group 1 (n = 13) received 3 monthly injections of 0.5 mg ranibizumab, Group 2 (n = 13) received 1 session of PDT and 3 monthly injections of ranibizumab, and Group 3 (n = 11) received 1 session of PDT and 1 injection of 4 mg triamcinolone. Retreatment, with the same therapeutic scheme in each group, was considered in case of persistence or recurrence of subretinal/intraretinal fluid. RESULTS: Twelve patients in Groups 1 and 2 and 9 patients in Group 3 completed the 3-year follow-up. A total of 58% of patients in Group 1, 50% in Group 2, and 88.9% in Group 3 had the same or better visual acuity at the end of the follow-up (P = 0.081). Patients in Group 3 exhibited considerable improvement in visual acuity (P = 0.032) and statistically significant decrease in central retinal thickness (P < 0.0001) than the 2 other groups at the end of the follow-up. Also, the patients in Group 3 received on average the lowest number of injections (P < 0.0001). Of note, geographic atrophy mainly at the place of previous retinal angiomatous proliferation lesion was detected in 0% in Group 1, 25% in Group 2, and 55.6% in Group 3 (P = 0.203), while 33.3% of patients in Group 1 developed retinal scar. CONCLUSION: Treatment with ranibizumab or ranibizumab plus PDT resulted in stabilization of the disease, while treatment with IVT plus PDT achieved better results in terms of functional and anatomical features compared with the other groups.

Intravitreal ranibizumab versus thermal laser photocoagulation in the treatment of extrafoveal classic choroidal neovascularization secondary to age-related macular degeneration.

BACKGROUND: To compare the efficacy of thermal laser photocoagulation versus intravitreal ranibizumab for the treatment of extrafoveal classic choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). METHODS: We conducted a retrospective study on 24 eyes with extrafoveal classic CNV secondary to AMD, treated either with thermal laser photocoagulation (group 1) or with intravitreal ranibizumab (group 2). Visual acuity, number of injections/sessions and recurrence rate were assessed. RESULTS: The mean follow-up time was 23.6 ± 2.26 and 19.1 ± 9.74 months for group 1 and 2, respectively. Mean best corrected visual acuity (BCVA) of groups 1 and 2 was 0.59 ± 0.32 and 0.46 ± 0.30 logMAR, respectively (p = 0.343). At the end of the follow-up, mean BCVA of group 1 was 0.92 ± 0.35 and of group 2 0.16 ± 0.12 logMAR and differed statistically compared to baseline (p = 0.02 and p = 0.006, respectively). There was a statistically significant difference between the two groups as far as BCVA at the end of the follow-up was concerned (p < 0.0001). The patients in group 1 received on average 1.38 sessions of thermal laser photocoagulation, while patients in group 2 received on average 4 injections of ranibizumab. The recurrence rate in the laser group was 84.6%, while in the ranibizumab group it was 18.2% (p < 0.001). Specifically, the mean time of recurrence in the laser group was 11.5 months, whereas in the ranibizumab group it was 18 months (p = 0.048). CONCLUSION: Intravitreal ranibizumab showed promising results in BCVA improvement and decrease in macular thickness in patients with extrafoveal classic CNV due to AMD, with a small number of injections. Laser photocoagulation treatment presented worsening in BCVA and high recurrence rate in our study with long-term follow-up.

Hemodialysis-induced alterations in macular thickness measured by optical coherence tomography in diabetic patients with end-stage renal disease.

BACKGROUND/AIMS: To evaluate changes in macular thickness measured by optical coherence tomography (OCT) during a hemodialysis (HD) session in diabetic patients with end-stage renal disease. METHODS: 72 eyes of 36 diabetic patients with and without macular edema were evaluated before and immediately after an HD session. Average and maximum macular thicknesses in the central disk (6 mm in diameter) and total macular volume were measured. RESULTS: In the eyes with diabetic macular edema, maximum macular thickness within the central disk of 6 mm, and mainly in its peripheral parts, was significantly reduced by 31.18 ± 4.18 µm after HD (p < 0.001). Average macular thickness and total macular volume were also significantly reduced (p = 0.003 and 0.015, respectively). In diabetic eyes without edema, maximum macular thickness decreased significantly by 11.21 ± 1.98 µm after HD (p < 0.001), while average macular thickness and total macular volume decreased slightly (p = 0.034, p = 0.043). Best-corrected visual acuity failed to change. We found a significant association of macular thickness changes with osmolality reduction and the presence of macular edema. CONCLUSION: HD decreases macular thickness in diabetic patients with macular edema, while there exists a less-pronounced effect in diabetic eyes without edema.

The significance of the external limiting membrane in the recovery of photoreceptor layer after successful macular hole closure: a study by spectral domain optical coherence tomography.

PURPOSE: To evaluate the external limiting membrane (ELM) by spectral domain optical coherence tomography (SDOCT) and its correlation with the inner segment/outer segment (IS/OS) line in patients with successful macular hole surgery. PROCEDURES: Forty-five eyes were divided into 3 groups according to the interval between surgery and first examination. In the first group the interval was between 6 and 12 months, in group 2 it was >12 months and ≤ 24 months, and in group 3 it was >24 months. The IS/OS and ELM of participants' eyes were postoperatively assessed using SDOCT in 2008 and 12 months later. RESULTS: A statistically significant association between the integrity of the ELM and the IS/OS junction line was observed in postoperative examinations in all 3 groups. Eyes with a complete IS/OS junction line had an intact ELM. Between the first and the second examinations, a significant improvement in best-corrected visual acuity (BCVA) was noted only in group 1. A positive statistical association was also observed in group 1 between restoration of the IS/OS junction line and improvement in BCVA over follow-up. CONCLUSIONS: The restoration of the IS/OS junction line is directly related to the integrity of the ELM.

Association of the preoperative photoreceptor layer defect as assessed by optical coherence tomography with the functional outcome after macular hole closure: a long follow-up study.

BACKGROUND: to evaluate the correlation between the extent of the inner/outer segment (IS/OS) defect preoperatively and improvement in postoperative best-corrected visual acuity (BCVA) associated with IS/OS line restoration. METHODS: forty-six eyes (46 patients) with successfully operated idiopathic full-thickness macular holes were studied using Stratus OCT3 with a mean follow-up of 34.7 months (range 24-60 months). The preoperative extent of the IS/OS junction defect, macular hole base diameter (MHBD) and BCVA were studied before surgery. The degree of IS/OS line restoration, macular thickness and BCVA were measured after treatment. RESULTS: the mean preoperative MHBD and IS/OS defect size were 783 and 1,973 µm, respectively. Postoperative continuity of the IS/OS junction was observed in 11 of 46 cases 12 months after treatment. In the remaining 35 patients, the IS/OS line was interrupted at 12 months of follow-up. The size of the preoperative IS/OS defect line was negatively correlated with the size of the postoperative IS/OS line and BCVA at 6 months and 12 months only (p < 0.0001). In all 46 eyes, the mean BCVA before and 12 months after treatment was 10 and 36.7 letters, respectively. BCVA remained almost unchanged after the first postoperative year of observation. CONCLUSIONS: the degree of reorganization of the photoreceptor layer after successful macular hole closure varies and is mostly related to the preoperative extent of the IS/OS defect line and the MHBD. A small-sized IS/OS preoperative defect favors improvement and restoration of the IS/OS line after treatment. The IS/OS junction line and BCVA are mostly restored during the first 12 months after treatment.

Optical coherence tomography findings in patients with retinitis pigmentosa and low visual acuity.

BACKGROUND AND OBJECTIVE: To study the morphological features of the macula of patients with retinitis pigmentosa and visual acuities of 20/200 or less as examined by optical coherence tomography. PATIENTS AND METHODS: In an observational case series study, 42 eyes (21 patients) with retinitis pigmentosa and visual acuities of 20/200 or less were evaluated by optical coherence tomography. RESULTS: Thirty-four (81%) eyes had atrophic retina (group 1) and 8 (19%) eyes had cystoid macular edema (group 2). The mean visual acuity was 20/1000 in group 1 and 20/300 in group 2. Epiretinal membrane was identified in 27 (64.3%) eyes. CONCLUSION: Optical coherence tomography is a more sensitive method in detecting macular pathology and can help in selecting cases where treatment may be applied.

Intravitreal administration of the anti-TNF monoclonal antibody infliximab in the rabbit.

BACKGROUND: Tumor necrosis factor (TNF) is known to play an important role in various immune-mediated ocular diseases; intravenous administration of the anti-TNF monoclonal antibody infliximab has proved beneficial in such cases. Since intravitreal injection (when available) is a substitute for systemic administration of various drugs targeting the eye, we aimed to evaluate the safety of intravitreal injection of infliximab in the rabbit eye. METHODS: Seven groups of New Zealand white rabbits (four animals in each group) received a single unilateral intravitreal injection (0.1 ml) of increasing doses of infliximab (namely 1, 2, 5, 8, 10 or 20 mg infliximab [Remicade]) or a sham injection respectively. Slit-lamp biomicroscopy, fundoscopy and electrophysiology recordings, i.e. scotopic, photopic and flicker responses, were performed at baseline and after 1, 5, 10, 15, 30 and 45 days. Infliximab-injected eyes were compared with sham-injected and with uninjected fellow eyes (n = 28). Animals were euthanized on day 45 for histopathological examination of the retinas. RESULTS: Clinical examination and electrophysiological testing were consistently unremarkable after either sham or 1 mg or 2 mg infliximab injections. In contrast, electrophysiological recordings were significantly reduced in a dose-dependent manner from day 1 through day 45, after 5, 8, 10 and 20 mg infliximab injections. Flicker responses were the most sensitive in detecting the lower toxic dose of 5 mg. Histopathological findings were similar in uninjected and sham-injected eyes, as well as after 1 mg or 2 mg infliximab injections. Consistent with the functional abnormalities, retinal deformities and diffuse edema were observed after injection of 5 mg or higher doses of infliximab. CONCLUSIONS: Intravitreal infliximab may be safely administered up to a dose of 2 mg in the rabbit eye. Such doses can be used in the design of future clinical trials assessing the effects of infliximab for selected patients with immune-mediated ocular conditions.

A rare case of peripheral ulcerative keratitis in temporal arteritis.

PURPOSE: To present a case of peripheral ulcerative keratitis (PUK) that progressed to corneal perforation in the setting of recently diagnosed temporal arteritis. METHODS: A 76-year-old man presented with a 2-week history of red eye and gradual loss of vision in the right eye. His medical history included recently diagnosed temporal arteritis without previous eye involvement. Clinical examination revealed severe peripheral corneal melting leading to corneal perforation. RESULTS: The patient was treated in the acute phase with topical dexamethasone drops and oral prednisolone. Perforation was sealed with cyanoacrylate glue. Azathioprine was also administered. Inflammation was resolved and his eye remains quiet. CONCLUSIONS: To our knowledge, this is the first reported case of PUK in the background of temporal arteritis.

Cystoid macular oedema within 24 h after a single application of latanoprost.

PURPOSE: To describe a patient who developed cystoid macular oedema (CMO) within 24 h after a single application of Latanoprost. METHODS: Observational case report. RESULTS: A 77-year-old man who had a previous cataract operation with vitreous loss in his left eye developed CMO 8 h after instillation of one drop of latanoprost. Five days after discontinuation of latanoprost the CMO resolved almost completely. Both the CMO and its resolution were documented with fluorescein angiography (FA) and optical coherence tomography (OCT). CONCLUSIONS: Latanoprost can lead to CMO even after a single application, as demonstrated in our case by FA and, in particular, by OCT. Caution is advised when administering the drug in high-risk eyes.

Inhibition of corneal neovascularization by subconjunctival bevacizumab in an animal model.

PURPOSE: To evaluate the effect of subconjunctival injection of bevacizumab on experimentally induced corneal neovascularization. DESIGN: Experimental animal study. METHODS: Twelve New Zealand white rabbits were involved, divided equally into four groups. Only one eye per rabbit was used. Topical instillation of 10 microl 5% NaOH solution was used, under general anesthesia, to induce corneal neovascularization secondary to corneal alkali burn in groups 2, 3, and 4. A single dose of 3.75 mg (25 mg/ml) bevacizumab was injected subconjunctivally. Group 1 (control group 1) was neither cauterized nor treated. Group 2 (control group 2) received a sham injection of balanced salt solution on day 14. Group 3 was treated on day 14 (after corneal neovascularization had been established). Group 4 was treated on day 1. Digital photographs were obtained and analyzed during the entire 28-day procedure. The area of neovascularization and scarring were measured in terms of the percentage of corneal surface affected. RESULTS: On day 28, the difference of neovascularization between groups 2, 3, and 4 was found to be statistically significant at the .05 level (one-way analysis of variance [ANOVA]): group 4 (4.7%+/-3.1%).1, one-way ANOVA). No side effects were noted. CONCLUSIONS: Subconjunctival administration of bevacizumab inhibits corneal neovascularization effectively in the rabbit experimental model, especially if administered early.