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.

A Pilot Study on Ocular Safety and Efficacy of Infliximab as an Antifibrotic Agent After Experimental Glaucoma Filtration Surgery.

INTRODUCTION: Tumor necrosis factor-α (TNF-α) is a multifunctional, proinflammatory cytokine that mediates pleiotropic biological functions, especially inflammation and immunoregulation. We hypothesized that blocking TNF-α with a monoclonal antibody would decrease inflammation and subconjunctival scarring in an animal model of experimental filtration surgery. METHODS: In a randomized, prospective, masked-observer study, 30 New Zealand albino rabbits underwent glaucoma filtration surgery. The animals were allocated to receive either intraoperative application of infliximab (group A) or mitomycin C (MMC) at a concentration of 0.2 mg/ml (group B) or balanced salt solution (BSS, control) (group C). Different infliximab doses, namely 1.0, 2.0, 3.0, 4.0, 5.0 mg in 0.1 ml, were applied. Bleb survival and characteristics were evaluated over a 30-day period. The animals were killed on postoperative day 15 or 30. Histology of the operated eyes was performed to evaluate and grade the amount of scarring in each group. Cellular density was evaluated in each case. RESULTS: Infliximab did not appear to improve outcomes in this model of glaucoma filtration surgery. Bleb survival was significantly higher in the MMC group compared to the other groups (p < 0.001 for both comparisons). Vascularity was also significantly lower in the MMC group compared to the other groups (p = 0.018 for both comparisons). There was a significant decrease in cellular density in the MMC group compared to the control (p = 0.0352) and the infliximab group (p < 001). CONCLUSION: Our results have shown that trabeculectomies in the infliximab group failed faster and displayed more scarring, compared to the control and MMC groups. This outcome suggests that the infliximab doses used in this pilot study resulted in a subconjunctival TNF-α concentration, which acted as a stimulator to fibroblasts.

Ambulatory Aortic Stiffness Is Associated With Narrow Retinal Arteriolar Caliber in Hypertensives: The SAFAR Study.

BACKGROUND: Arterial stiffness measured under static conditions reclassifies significantly cardiovascular (CV) risk and associates with narrower retinal arterioles. However, arterial stiffness exhibits circadian variation, thus single static stiffness recordings do not correspond to the "usual" 24 hr, awake, and asleep average arterial stiffness. We aimed to test the hypothesis that ambulatory 24 hr, awake, and asleep aortic (a) pulse wave velocity (PWV) associate with retinal vessel calibers, independently of confounders and of static arterial stiffness, in hypertensive individuals free from diabetes and CV disease. METHODS: Digital retinal images were obtained (181 individuals, age: 53.9±10.7 years, 55.2% men) and retinal vessel calibers were measured with validated software to determine central retinal arteriolar and venular equivalents (CRAE and CRVE, respectively); ambulatory (24 hr, awake, asleep) and static office aPWV were estimated by Mobil-O-Graph; and static office carotid to femoral (cf) PWV by SphygmoCor. RESULTS: Regression analysis performed in 320 gradable retinal images showed that, after adjustment for confounders: (i) ambulatory aPWV was significantly associated with narrower retinal arterioles but not with venules; (ii) asleep aPWV had stronger associations with CRAE than awake aPWV; (iii) both ambulatory aPWV and cfPWV were associated mutually independently with narrower retinal arterioles; aPWV introduction in the model of cfPWV, improved model's R2 (P = 0.012). Similar discriminatory ability of 24 hr aPWV and of cfPWV to detect the presence of retinal arteriolar narrowing was found. CONCLUSION: Ambulatory aPWV, estimated by an operator-independent method, provides additional information to cfPWV regarding the associations of arterial stiffness with the retinal vessel calibers.

The Keith-Wagener-Barker and Mitchell-Wong grading systems for hypertensive retinopathy: association with target organ damage in individuals below 55 years.

BACKGROUND: The usefulness of the hypertensive retinopathy classification by Keith-Wagener-Barker (KWB) in clinical practice remains controversial. The simplified Mitchell-Wong grading, combining the two initial KWB' grades in one stage, is proposed as an alternative method; both systems are poorly validated regarding their association with target organ damage. OBJECTIVE: In a population free of cardiovascular disease and diabetes, we aimed to investigate the interobserver and intraobserver agreement of both grading systems, their association with aortic stiffness, carotid hypertrophy or plaques and the role of age and sex on this association. METHODS: Digital retinal images were obtained and graded - according to both classifications - by two independent and blinded observers; aortic stiffness (carotid-femoral pulse wave velocity, m/s) and common carotid hypertrophy (cross-sectional area, mm) or plaques were assessed by tonometry and ultrasound, respectively. RESULTS: From the gradable retinal photos obtained by 200 eyes of 107 consecutive patients (age: 54 ±â€Š13 years, 51% men, 79% hypertensive patients) and after adjustments for confounders, the intraobserver and interobserver level of agreement was as following: KWB 88/64% and Mitchell-Wong 91/71%, respectively; exclusively in younger, not older, individuals aortic stiffness, carotid hypertrophy, but not plaques, were significantly associated with both systems, independently from confounders; no differences regarding target organ damage were found between stages 1 and 2 of KWB. CONCLUSION: Detecting early signs of hypertensive retinopathy may be of value in young individuals; the Mitchell-Wong seems preferable to the KWB classification system only for reasons of simplifying clinical practice.

Macular buckling in optic disc pit maculopathy in association with the origin of macular elevation: 13-year mean postoperative results.

PURPOSE: To discuss the anatomical and functional results in cases of optic disc pit maculopathy (ODP-M) with a follow-up of at least 11 years after scleral buckling procedure (SBP). METHODS: We studied 12 eyes with ODP-M treated with SBP, in a long-term follow-up of 12.8 ± 1.5 years after surgery. All patients underwent best-corrected visual acuity (BCVA) measurement, slit-lamp biomicroscopy, fundus photography, fluorescein angiography, indocyanine green angiography, B-scan ultrasonography, and optical coherence tomography at baseline and 6-12 months, 2 years and at least 11 years postoperatively. RESULTS: Complete macular reattachment was noticed between 6 and 12 months postoperatively. The BCVA improved significantly at the first postoperative examination. Further improvement was noticed at the second examination, while BCVA remained almost stable at the last examination. Foveal restoration of ellipsoid layer (inner segment/outer segment) was noted in 10 out of 12 cases. The existing vitreous strands remained unchanged during the follow-up. Vitreous traction gradually disappeared (4/5 eyes). Circulation in short/long posterior ciliary arteries was unaffected, while neither recurrences nor complications were observed during the follow-up period. Association of the scleral sponge to the scleral sheath of the optic nerve remained unchanged during the follow-up. CONCLUSIONS: A total of 12.8 ± 1.5 years after treatment, all the studied cases retained the successful anatomical and functional results that they had 2 years postoperatively, without inducing cataract during the follow-up period. The SBP seems to act equally well as a barrier either obstructing the entrance of fluid from the vitreous cavity or blocking the circulation of subarachnoid cerebrospinal fluid into the retina.

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.

Correlation between optic nerve head parameters, RNFL, and CCT in patients with bilateral pseudoexfoliation using HRT-III.

BACKGROUND: It is well-established that eyes with pseudoexfoliation syndrome (PXS) have higher intraocular pressure (IOP). Early diagnosis of preperimetric glaucoma will assist with better management of these patients. The aim of this study is to evaluate the optic nerve head (ONH) parameters and retinal nerve fiber layer (RNFL) thickness in subjects with bilateral PXS, bilateral pseudoexfoliative glaucoma (PXG) and normal, correlating these results with central corneal thickness (CCT). DESIGN: This is a cross-sectional, case control study. All participants were from the Department of Ophthalmology, Athens University Medical School. PARTICIPANTS: A total of 55 eyes from 55 patients with PXS (27 eyes from 27 patients with PXG and 28 eyes from 28 normal subjects) were studied. METHODS: Topographic measurements of the ONH and peripapillary RNFL thickness were performed using a confocal scanning laser ophthalmoscope (the Heidelberg Retina Tomograph-III). The outcomes were correlated with the CCT of the subjects. MAIN OUTCOME MEASURES: PXS subjects and age-matched normal subjects did not differ significantly in ONH parameters. RNFL thickness was significantly lower in the PXS group compared with the normal group, but there was not a statistically significant difference with the PXG patients. Regarding the correlation with CCT, the PXG group showed negative correlation with mean (p = 0.027) and max cup depth (p = 0.031), while PXS subjects revealed a positive correlation with RNFL thickness (p = 0.032). CONCLUSIONS: Our study showed that PXS subjects may be at greater risk of RNFL thinning, presenting a statistically significant positive association of the latter parameter with the CCT.

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.

Spontaneous resolution of vitreomacular traction demonstrated by spectral-domain optical coherence tomography.

PURPOSE: To evaluate the natural course of idiopathic vitreomacular traction (VMT) with spectral-domain optical coherence tomography (SDOCT) from the vitreomacular adhesion (VMA) stage to the spontaneous resolution of VMT. DESIGN: Prospective observational case series. METHODS: We studied the natural course of idiopathic VMT in 46 eyes (46 patients), divided into those that proceeded to spontaneous VMT resolution (12 cases) and those that remained at the VMT stage (34 cases). All patients were examined with SDOCT at regular 3-month intervals. We recorded the vitreomacular angle of VMA nasally and temporally, the horizontal diameter of VMA, macular thickness, visual acuity, photoreceptor layer, and external limiting membrane. RESULTS: In the 12 eyes that proceeded to spontaneous resolution, the vitreous adhesion angle had a mean increase of 38 degrees at VMT, compared to the angle at the VMA stage. In the 34 eyes that remained at the VMT stage, the mean angle of traction increased by only 1 degree throughout follow-up. In all 46 patients, the angle at the VMT stage was significantly associated with traction resolution (nasally P = .001, temporally P < .001). The likelihood of resolution was more than 99% lower for patients with a VMT diameter >400 µm compared with that of eyes with a VMT diameter <400 µm. Patients with broad-type VMT remained at the same stage, whereas patients with V-type VMT had 80% probability of resolution. CONCLUSIONS: Spontaneous VMT resolution is negatively associated with the horizontal adhesion diameter. The strength of the traction exerted by the vitreous on the fovea seems to be positively related to the size of the vitreomacular angle.

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.

Photoreceptor layer changes overlying drusen in eyes with age-related macular degeneration associated with vitreomacular traction.

PURPOSE: To investigate by spectral-domain optical coherence tomography (SD-OCT) changes of photoreceptor layers over drusen in cases of dry type age-related macular degeneration associated with vitreomacular traction (VMT). METHODS: Clinical examination, fluorescein angiography, fundus photography, and SD-OCT data were retrospectively studied for a consecutive series of 27 patients with drusen, pseudodrusen, and VMT. Control groups of 32 patients with VMT without drusen and 34 patients with drusen and pseudodrusen without VMT were also studied. RESULTS: The examination revealed disruption of the line corresponding to the inner segment ellipsoid (ISel), previously called inner segment/outer segment junction, of photoreceptor layer, and development of cystoid edema in significantly higher incidence in VMT associated with drusen group. 22 out of 32 eyes with VMT and drusen (68.75%) had disrupted ISel, compared to 8 out of 37 (21.6%) control eyes with drusen only and to 12 out of 37 (32.4%) control eyes with VMT only. Chi-square analysis showed significant association between drusen and pseudodrusen on fovea, VMT, and localization of ISel disruption. The changes of the ISel were mainly found in the area that corresponded to VMT. The SD-OCT revealed drusen throughout the macula and discontinuation of ISel only in the fovea in 4 of 32 (12.5%) eyes with VMT, whereas none of 37 control eyes with drusen only had similar appearance. CONCLUSIONS: The drusen in association with the cystoid macular edema induced by vitreous traction contribute to the photoreceptor layer defect overlying drusen in the fovea. In addition, the number of drusen and pseudodrusen was increased in the area of the vitreous traction compared to the peripheral retina.

The effect of subconjunctival ranibizumab on corneal and anterior segment neovascularization: study on an animal model.

PURPOSE: To evaluate the effect of subconjunctival anti-vascular endothelial growth factor (VEGF) ranibizumab on corneal and anterior segment neovascularization. METHODS: In this experimental study and laboratory investigation, chemical cauterization was utilized to induce corneal neovascularization in 16 rabbits randomly divided in 2 equal groups. Cauterized eyes were either treated with 0.1 mL (1 mg) of subconjunctival ranibizumab or administered a sham injection. A third group of 4 rabbits served as control for side effects after ranibizumab administration. All animals were monitored daily for 14 days and the extent of corneal scarring and neovascularization was measured on days 1, 7, and 14. After enucleation, ocular tissues were separated under a surgical microscope and VEGF levels were measured with ELISA. Statistical analysis was performed to compare the extent of corneal neovascularization and VEGF levels between treated and untreated eyes. RESULTS: Subconjunctival ranibizumab inhibited corneal neovascularization significantly both in the first and the second week compared to untreated controls (p = 0.006 and p = 0.001, respectively). The VEGF levels were significantly lower in all anterior segment tissues like the cornea, iris, aqueous humor, and conjunctiva of the treated eyes (p<0.01). The reduction of VEGF levels ranged from 19% to 73% in different ocular tissues. Corneal scarring was not significantly affected by anti-VEGF treatment (p = 0.7). No side effects were noticed. CONCLUSIONS: Early subconjunctival administration of ranibizumab may successfully inhibit alkali-induced corneal neovascularization in an animal model. Subconjunctival ranibizumab reduces VEGF levels significantly not only in the cornea and the bulbar conjunctiva but also in the aqueous humor and the iris.

Comparison of SWAP and SAP on the point of glaucoma conversion.

BACKGROUND: The purpose of this study was to compare the two perimetric modalities, SWAP (short wavelength automated perimetry) and SAP (standard automated perimetry), on the point of conversion to glaucoma. METHODS: In this prospective, longitudinal, follow-up study, 282 patients with ocular hypertension were recruited consecutively and tested with both SAP and SWAP annually for 5 years or until the onset of conversion to glaucoma. SAP and SWAP perimetry was performed with the Humphrey Field Analyzer II using the 24-2 full-threshold test. Abnormality for both SAP and SWAP fields was determined on the pattern deviation plot and defined as either a) one point below the 0.5% probability level or b) a cluster of 2 or more points below 1% or c) a cluster of 3 or more points below 2% or d) a cluster of 4 or more points below 5%. Abnormal tests had to be confirmed on a subsequent test within one year to be classified as conversion. RESULTS: Of the 282 patients initially recruited, 32 were excluded. Of the 250 remaining patients, a total of 38 converted during the follow-up period; 36.8% of conversions were detected earlier with SWAP, 29% simultaneously, and 34.2% were not detected with SWAP during the follow-up period; 2.4% of patients showed SWAP visual field loss that did not result in conversion during the follow-up period. CONCLUSION: The results in our study are inconclusive. There were patients with earlier, simultaneous, or no SWAP conversion, with SAP conversion as the golden standard criterion. One should consider both SAP and SWAP with confirmation when visual field loss is evident to maximize early detection of glaucoma, because it appears that each method identifies early glaucoma in a subset of patients and these subsets overlap only partially.

Dry eye in Graves ophthalmopathy: correlation with corneal hypoesthesia.

PURPOSE: To evaluate dry eye disease and corneal sensitivity in patients with early and active Graves ophthalmopathy (GO). METHODS: A total of 52 eyes of 26 patients with early GO and 74 eyes of 37 age- and sex-matched controls were included in our study. Dry eye disease was assessed based on the criteria of the International Dry Eye Workshop. Diagnosis of early GO was based on the European Group on Graves' Orbitopathy consensus statement. Clinical Activity Score (CAS) and Werner-NOSPECS Score were determined. Corneal sensitivity was assessed using a Cochet-Bonnet aesthesiometer. RESULTS: A total of 67.8% of patients with early GO and 13.5% of healthy controls had ocular surface dryness (p<0.001). The mean Schirmer test score was significantly lower in patients with early GO (12.88 ± 7.94 mm [right eyes] and 14.04 ± 9.00 mm [left eyes]) than in controls (18.08 ± 7.26 mm [right eyes] and 18.05 ± 7.50 mm [left eyes] [p<0.05]). The tear film break-up time was lower in patients by 5.46 seconds and 5.74 seconds in right and left eyes (p<0.001). We also found a significant reduction in corneal sensitivity in patients with early GO (4.16 ± 0.68 [right eyes] and 4.10 ± 0.89 [left eyes]) than in controls (4.70 ± 0.34 [right eyes] and 4.72 ± 0.34 [left eyes] [p<0.05]). The CAS correlated significantly with the Schirmer test (r = -0.60, p = 0.003). CONCLUSION: Dry eye is common in early GO even in the absence of apparent exophthalmos and is associated with CAS and reduced corneal sensitivity.