The effect of intravitreal anti-vascular endothelial growth factor injections on corneal endothelium in patients with diabetic macular oedema.

PURPOSE: To evaluate the characteristics of corneal parameters in patients with diabetic macular oedema (DME) treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. METHODS: Participants in this study were 36 patients with DME, treated with either intravitreal ranibizumab (n = 16) or aflibercept (n = 20). All participants underwent best-corrected visual acuity (BCVA) measurement, optical coherence tomography and non-contact specular microscopy to evaluate corneal endothelium parameters (endothelial cell density-ECD, hexagonality, coefficient of variation of the cell size and central corneal thickness-CCT), at baseline and at months 6 and 12 after the first intravitreal injection. Comparisons between baseline and months 6 and 12 were performed. RESULTS: There was no statistically significant difference regarding ECD, hexagonality, coefficient of variation of the cell size and CCT at month 6 and 12 post initial injection compared to baseline in patients with DME. BCVA improved significantly at month 6 and 12 compared to baseline (p < 0.001 for both comparisons). Central retinal thickness was significantly reduced at month 6 and 12 compared to baseline (p < 0.001 for both comparisons). CONCLUSION: Intravitreal anti-VEGF injections in patients with DME were found not to affect corneal parameters, namely ECD, hexagonality, coefficient of variation of the cell size and CCT at the long-term follow-up of 12 months.

The Effect of Diabetes Mellitus on Corneal Endothelial Cells and Central Corneal Thickness: A Case-Control Study.

PURPOSE: The aim of this study was to evaluate the characteristics of corneal endothelial cells and central corneal thickness (CCT) in patients with diabetes mellitus (DM), comparing them with those of healthy subjects (controls) and to determine potential factors affecting the corneal parameters in patients with DM. METHODS: Participants in this study were 72 patients with DM and 88 healthy controls. Diabetic patients were further classified into groups depending on the severity of diabetic retinopathy (no retinopathy, mild, moderate, severe non-proliferative diabetic retinopathy, and proliferative diabetic retinopathy). All participants underwent non-contact specular microscopy to evaluate corneal endothelium parameters and CCT, while factors affecting endothelial cell density and CCT in patients with DM were also analyzed. RESULTS: Patients with DM presented significantly decreased endothelial cell density compared to controls (2,297.9 ± 311.3 and 2,518.3 ± 243.7 cells/mm2, respectively; p < 0.001), while the two groups did not differ significantly in any other measured corneal parameter. In the diabetic group, the multivariate analysis showed a significant association between decreased endothelial cell density and increased HbA1c (p < 0.001), longer DM duration (p = 0.003), and more severe diabetic retinopathy status (p = 0.008). CONCLUSION: DM seems to affect the corneal endothelium, since endothelial cell density was decreased in the diabetic group, while duration of disease, HbA1c levels, and severity of retinopathy were significantly associated with changes in endothelial cell density and should be taken into account.

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.

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 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.

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.

An atypical case of herpes simplex virus endotheliitis presented as bullous keratopathy.

PURPOSE: To present an atypical case of herpes simplex virus (HSV) endotheliitis. METHODS: The authors report the case of a 62-year-old female patient who presented with unilateral diffuse corneal edema with Descemet's membrane folds and bullae, without keratic precipitates, iritis, significant anterior chamber reaction, or intraocular pressure (IOP) elevation. The patient had no documented positive history of ocular surgery and no abnormal findings were present in the fellow eye. Endotheliitis of viral origin was suspected and Goldmann-Witmer coefficient for HSV, cytomegalovirus, and varicela zoster virus was calculated. RESULTS: Goldmann-Witmer coefficient was positive for HSV. Treatment with oral valacyclovir and topical dexamethasone resulted in complete resolution of corneal edema within 1 week. CONCLUSIONS: HSV endotheliitis can present with bullous keratopathy as the only clinical manifestation, without typical findings such as keratic precipitates, iritis, and IOP elevation.

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.

Unusual case of orbital apex syndrome after chalazion excision.

Orbital apex syndrome represents a heterogeneous group of disorders. It involves damage to the third, fourth and sixth nerves and the ophthalmic division of the fifth cranial nerve, and results in optic neuropathy. An 80-year-old man presented to our emergency clinic with left acute visual loss and three-day history of ocular pain. His medical and ophthalmic history involved diagnosis of lung cancer and chalazion excision two weeks prior to presentation. There was total left ophthalmoplegia, vision was 'no light perception' and he had a relative afferent pupillary defect. An urgent computed tomography scan of the orbits showed sub-periosteal abscess on the lateral wall of the orbit extending to the optic canal. The muscle cone was unaffected. The diagnosis was orbital apex syndrome. He underwent urgent drainage of the abscess and Staphylococcus aureus was identified with Gram stain. He was systemically administered intravenous antibiotics and steroids. His visual acuity and ophthalmoplegia improved rapidly 12 hours after surgery. Prompt diagnosis and treatment in cases of orbital apex syndrome, especially in immunocompromised patients, is important to prevent visual and life-threatening complications.

Effect of aminoguanidine on the conjunctival histamine and nitrite levels in experimental conjunctivitis.

PURPOSE: Histamine and nitric oxide (NO) play pivotal roles in ocular surface hypersensitivity reactions, whereas the activity of their metabolic enzymes diamine oxidase (DAO) and NO synthase (NOS) may affect their function. This study aimed at investigating the effects of ocular administration of aminoguanidine (AMG), a multiple action DAO and NOS inhibitor, on the conjunctival histamine and nitrite levels in a model of experimental conjunctivitis. METHODS: AMG, at 0.81, 81 or 81×10(3) µM, was instilled into the lower conjunctival fornix of normal and compound 48/80 (C48/80)-challenged eyes of male Wistar rats in the absence or presence of 40 mg/mL disodium cromoglycate. Histamine and nitrite were quantified in the conjunctival homogenate and lavage fluid 45 min and 6 h postchallenge, respectively. RESULTS: AMG induced no significant alterations in basal histamine and nitrite levels in the normal rat eye. In experimental conjunctivitis, AMG failed to modify the reduction in histamine content and partially circumvented the increases in nitrite levels observed during the early and late phase reactions, respectively. In the presence of disodium cromoglycate, AMG significantly increased the levels of both proinflammatory mediators in the normal rat eye. CONCLUSIONS: The data suggested that DAO may not be the main route of in situ histamine catabolism in the normal and C48/80-challenged rat conjunctiva, whereas NOS contributes to the phenotypic alterations observed in mast cell-dependent conjunctivitis. Mast cell stabilizing agents and AMG-modulated systems seem to interact through yet undefined mechanisms in the different phases of ocular hypersensitivity reactions.

Intraoperative complication during phacoemulsification in patient with epidermolysis bullosa.

UNLABELLED: We report the case of a 56-year-old woman with known recessive dystrophic epidermolysis bullosa and an unremarkable ocular history who experienced an extensive corneal epithelial blister during phacoemulsification cataract surgery. To our knowledge, this is the first report of this complication. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Peripheral ulcerative keratitis in a patient with systemic-onset juvenile idiopathic arthritis.

The recognition of ocular manifestations in juvenile idiopathic arthritis is critical. The authors report an unusual manifestation of corneal involvement in a 10-year-old girl with systemic-onset juvenile idiopathic arthritis who presented with unilateral peripheral ulcerative keratitis during arthritis exacerbation. Corneal inflammation was successfully managed with topical steroids, oral methylprednisolone, and methotrexate.

Vitrectomy for treatment of a lamellar hole in a patient with exudative macular degeneration: the role of vitreous traction elimination.

PURPOSE: Lamellar macular hole (LMH) represents a well-defined clinical entity with variable pathophysiologic mechanisms and a controversial therapeutic approach. The purpose of the present work is to present a patient with an epiretinal membrane (ERM)-associated LMH on the background of exudative age-related macular degeneration (AMD) that was successfully managed with pars plana vitrectomy. METHODS: Interventional case report. RESULTS: A 67-year-old man presented with progressive visual loss OS of 5 months' duration. He was diagnosed with an ERM-associated LMH with coexisting subretinal fluid arising by a neovascular membrane on the background of exudative AMD confirmed with fundus fluorescein angiography. He underwent a 3-port pars plana vitrectomy with ERM-internal limiting membrane peeling and gas tamponade (14% C3F8) for treatment of the LMH and ERM with a view to undergo anti-vascular endothelial growth factor treatment for the exudative AMD. Postoperative optical coherence tomography demonstrated complete closure of the LMH with simultaneous total subretinal fluid absorption that was maintained at the 2-month follow-up period. CONCLUSIONS: To our knowledge, this is the first report whereby pars plana vitrectomy in a patient with an ERM-associated LMH on the background of exudative AMD resulted in improvement of both clinical entities. The latter strengthens the role of vitreous traction elimination in exudative AMD and highlights the need for further research.

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.

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.

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 + or - 0.75 months) after the initiation of treatment in the fellow eye compared with 33.25 + or - 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.