Miltiadis Papathanassiou

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%)<group 3 (13.3%+/-2.3%)<group 2 (41.0%+/-3.6%; P<.05, Mann-Whitney U test). In group 3, the area of neovascularization decreased 14 days after treatment by 42%. Neovascularization was almost completely absent in group 4. The development of scarring was unaffected by bevacizumab (P>.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.

Corneal Collagen Cross-Linking for Infectious Keratitis: A Systematic Review and Meta-Analysis.

Purpose: To assess the efficacy of corneal collagen cross-linking (CXL) in the management of infectious keratitis. Methods: Comprehensive literature search was performed in MEDLINE/PubMed and Cochrane Central Register of Controlled Trials using combinations of the following search terms: “corneal collagen cross linking” or “photoactivated riboflavin” or “UVA light and riboflavin” and “infectious keratitis” or “corneal ulcer.” Last search was on March 19, 2015. Extracted data from individual studies were summarized and summary proportions of eyes healed and complications for different subgroups were estimated. Results: Twenty-five studies were included (2 randomized controlled trials, 13 case series, and 10 case reports) with a total of 210 eyes of 209 patients, of which 175 eyes underwent CXL. Causative microorganisms were bacteria, fungi, acanthamoeba, and Herpes simplex virus in 96, 32, 11, and 2 cases, respectively. Coinfections were present in 13 and cause was inconclusive in 21 cases. Sixteen of 175 eyes received no additional antibiotics, whereas 159 underwent CXL as an adjunct to antimicrobial treatment. Proportion of eyes healed with CXL was 87.2% (95% confidence interval (CI), 81.9%, 91.8%). For bacterial keratitis, the proportion of eyes healed was 85.7% (95% CI, 78.5%, 91.7%), whereas 10/11 and 25/32 eyes with acanthamoeba and fungal keratitis, respectively, were healed (available data not sufficient to provide a valid proportion analysis). Treatment resulted in corneal melting and tectonic keratoplasty in both Herpes simplex virus cases. Conclusions: CXL seems promising in the management of infectious keratitis, excluding viral infections. However, more randomized controlled trials are required to assess its efficacy.

The Effect of Intravitreal Ranibizumab on the Fellow Untreated Eye with Subfoveal Scarring due to Exudative Age-Related Macular Degeneration

Aim: Our purpose was to evaluate the possible effect of intravitreal ranibizumab on the fellow untreated eye with choroidal neovascularization (CNV) and subfoveal scarring associated with age-related macular degeneration (AMD). Methods: A retrospective observational study was conducted. One hundred eighty-seven ranibizumab-treated patients diagnosed as having subfoveal CNV scarring in the untreated eye were compared with a control group of untreated unilateral subfoveal CNV scarring. Inclusion criteria concerning treated eyes in the ranibizumab group complied with the MARINA and ANCHOR studies. Demographic data, clinical course, visual acuity, fluorescein angiography and optical coherence tomography findings were evaluated. Results: Clinical improvement was confirmed in 24% of the patients in the ranibizumab group and in only 12.9% of the controls. Improvement was noted as early as 2–4 months (2.83 ± 0.75 months) after the initiation of treatment in the fellow eye compared with 33.25 ± 9.43 months in the control group (p = 0.01; Mann-Whitney U test). Kaplan-Meier curves demonstrate the positive impact of ranibizumab on the visual acuity of the fellow untreated eye (p = 0.016; Log-Rank test). Conclusions: Ranibizumab might induce some therapeutic effect in selected cases of end-stage CNV scarring, which needs to be further examined. The VEGF levels in the compartments of the fellow eye of patients with age-related macular degeneration treated with ranibizumab need to be further evaluated.

Vascular endothelial growth factor inhibitors for treatment of corneal neovascularization: a meta-analysis.

Purpose: To evaluate the therapeutic effect of bevacizumab (Avastin) on corneal neovascularization (NV). Methods: Systematic review and meta-analysis of the literature was performed. Seven eligible clinical human studies and 18 eligible experimental animal studies examining the effectiveness of bevacizumab treatment on corneal NV were included in the meta-analysis. Pertinent publications were identified through a systematic search of PubMed. All references of relevant reviews and eligible articles were also screened, and data were extracted from each eligible study. The random-effects model (of DerSimonian and Laird) was used to combine the results from the selected studies. Heterogeneity was explored using available data. Publication bias was also assessed. Results: A significant reduction of corneal neovascularized area was seen in clinical human studies, with a pooled reduction of 36% [95% confidence interval (CI), 18%–54%] overall, of 32% (95% CI, 10%–54%) for subconjunctival anti–vascular endothelial growth factor injections, and 48% (95% CI, 32%–65%) for topical treatment. Pooled mean change in best-corrected visual acuity showed an improvement in best-corrected visual acuity by 0.04. The summary standardized mean difference in animal studies indicated a statistically significant reduction in the area of corneal NV when treated with bevacizumab compared with the control group by −1.71 (95% CI, −2.12 to −1.30). The subtotal pooled standardized mean differences were −1.83 (95% CI, −2.38 to −1.28) for subconjunctival anti–vascular endothelial growth factor injections and −1.50 (95% CI, −1.88 to −1.12) for topical treatment. Conclusion: Our results suggest that both topical and subconjunctival bevacizumab achieve significant reduction in the area of corneal NV. This meta-analysis provides an evidential basis for the new therapeutic concept of treating corneal NV with antiangiogenic therapy.

Leukotriene antagonists attenuate late phase nitric oxide production during the hypersensitivity response in the conjunctiva.

AbstractObjective:To investigate the role of cysteinyl leukotrienic (cysLT) antagonists on conjunctival nitric oxide (NO) release in experimental allergic conjunctivitis. Methods:Zafirlukast, disodium cromoglycate or levocabastine were instilled into the C48/80-challenged eyes of male Wistar rats. The conjunctival histamine content and nitrite levels in the lavage fluid were quantified 45 min and 6 h post-challenge, respectively. Instillation of phosphate buffer saline reflected control treatment. Statistical analyses were performed by ANOVA. Results:Topical challenge with C48/80 significantly altered the histamine and nitrite levels to 44.6 ± 2.8% and 233 ± 19% of the control (P < 0.01), respectively. Instillation of zafirlukast, disodium cromoglycate or levocabastine reversed the effect of C48/80 on nitrite release, its levels being 150 ± 27%, 54 ± 14% and 121 ± 20% of the control (P > 0.05), respectively. Zafirlukast had no effect on the histamine content. Conclusions:By inhibiting the late-phase NO component of the conjunctival hypersensitivity response, cysLT antagonists might contribute to the management of ocular inflammatory responses.

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, mm2) 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 ± 13 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.

Pharmacokinetics of intravenously administered moxifloxacin in eye compartments: an experimental study

The purpose of this study was to evaluate the pharmacokinetics of intravenously administered moxifloxacin, a fourth-generation fluoroquinolone, in different parts of the non-inflamed eye. Moxifloxacin was administered intravenously at a dose of 20mg/kg moxifloxacin over 30min. Sampling of peripheral blood, aqueous humour and vitreous was performed at standard time intervals post infusion once in each animal. Moxifloxacin levels were estimated by high-performance liquid chromatography with fluorescence detection. Mean serum concentrations were 3.43, 2.74, 1.48 and 1.12microg/mL at 0.5, 3, 6 and 24h after the end of drug infusion, respectively. Respective concentrations in aqueous humour were 2.44, 2.03, 1.30 and 1.09microg/mL and in vitreous body they were 1.68, 1.87, 1.78 and 1.15microg/mL. It is concluded that systemic administration of moxifloxacin in rabbits was accompanied by efficient penetration into both the aqueous humour and the vitreous body at concentrations well above the minimum inhibitory concentration for most causative pathogens of endophthalmitis. Further research is mandatory to clarify the clinical significance of these findings.

Exemestane-induced corneal epithelial changes

We report a case of corneal epithelial changes that occurred as ocular side effects of treatment with exemestane, a selective steroidal aromatase inhibitor. A 55-year-old woman presented to our outpatient department for routine eye examination. Clinical examination revealed bilateral corneal gray-white bands appearing as intraepithelial microcysts. Her past medical history included breast cancer, for which she underwent chemotherapy and subsequent treatment with exemestane. She was followed up for 1 year, during which the clinical picture of the cornea remained unchanged in both eyes and visual acuity remained unaffected. A causal connection seems to be possible between systemic treatment with exemestane and persisting corneal intraepithelial cysts.

Corneal melt in lattice corneal dystrophy type II after cataract surgery

We report a patient with lattice corneal dystrophy type II, also known as Meretoja syndrome or familial amyloidosis Finnish type, who developed a corneal melt 15 days after uneventful phacoemulsification. Despite conservative treatment, the corneal melt resulted in perforation. Uneventful penetrating keratoplasty was performed, but delayed graft epithelial healing was noticed postoperatively. Corneal button histopathological evaluation confirmed the initial clinical diagnosis. To our knowledge, this is the first reported case of corneal melt and perforation in a patient with lattice corneal dystrophy type II.

Macular hole formation following phacoemulsification cataract surgery

Idiopathic full-thickness macular holes develop as a result of antero-posterior and tangential traction exerted by the posterior vitreous cortex at the fovea. Although full-thickness macular holes (FTMH) were originally described in the last century, in relation to trauma, inflammation and myopia, more recent clinical studies have shown that the vast majority is idiopathic. Macular holes are more common in women and have been classified in four stages: 1. Stage 1 is also termed an impending hole and is characterised by progressive loss of the foveal depression. The visual acuity at this stage is reasonably good. 2. When further traction results in the formation of a foveal hole or dehiscence associated with a cuff of subretinal fluid, the hole is characterised as stage 2 and the visual acuity usually deteriorates to a level of 6/12 to 6/30. 3. In stage 3, the macular hole is fully developed and there is no posterior vitreous detachment (PVD). Stage 3 holes are usually associated with acuity levels of 6/18 to 6/60. 4. When posterior vitreous detachment occurs the hole is characterised as stage 4. Macular hole as a complication of phacoemulsification is a rare entity. The implicated pathophysiology is not yet completely understood and it appears to be multifactorial. Here, we report two cases of macular hole formation following phacoemulsification, each one following a different path in the pathophysiological pathway.