Murat Hasanreisoglu

Molecular and histological changes following central retinal artery occlusion in a mouse model

The aim of this study was to characterize the molecular and histological changes that occur in the retina following central retinal artery occlusion (CRAO) in a mouse model. CRAO was induced in 60 mice by laser photoactivation of intravenously injected rose bengal. Mice were sacrificed at 3, 6, 12, and 24h and 7 and 21 days after CRAO induction for molecular analysis (5-13 mice/time point) and histological and apoptosis studies (3-4 mice/time point). Fundus examination and fluorescein angiography were also performed at various points. Retinal mRNA was analyzed for expression of T-cell antigen 1 (Thy-1), vascular endothelial growth factor (VEGF), heme oxygenase-1 (HO-1), and hypoxia-induced factor 1 alpha (HIF-1 alpha) using real-time polymerase chain reaction. The results showed that at 6-24h following CRAO induction, the retina was edematous, with interrupted blood perfusion. Fluorescein angiography showed reperfusion at 6h, and TdT-mediated dUTP nick end-labeling (TUNEL) assay revealed an increase in apoptotic cells in the first 24h. On histological sections, nuclear loss in the inner retinal layers was maximal on day 21. Thy-1 expression decreased to 30% of baseline (P<or=0.002). VEGF expression increased in the first 3h and gradually decreased thereafter, reaching 75% of baseline on day 21 (P<or=0.005). HO-1 was upregulated at all time points, with a peak at 12h. No change was noted in HIF-1 alpha expression at any time. In conclusion, CRAO in mice causes cell apoptosis in the inner layers of the retina, with a significant cell loss and a decrease in Thy-1 expression by 21 days. These changes are accompanied by a rise in expression of the ischemia-related protein HO-1 to a peak at 12h, with levels remaining above control values at day 21. Given the similarity of the mouse model to human CRAO, these findings may have implications for the future clinical management of CRAO.

Retinal Metastasis From Systemic Cancer in 8 Cases

IMPORTANCE Metastatic tumors of the retina are rare, simulate retinitis, and are associated with poor patient survival. OBJECTIVE To describe the clinical features and outcomes of patients with retinal metastasis from systemic cancer. DESIGN, SETTING, AND PARTICIPANTS Retrospective case series of 8 patients with retinal metastasis from cutaneous melanoma (n = 4), breast cancer (n =2), esophageal cancer (n =1), and lung cancer (n = 1). At presentation, the mean patient age was 62 years and all were white. INTERVENTION Treatment included plaque radiotherapy (n = 1) for localized disease or enucleation (n =3) for extensive tumor hemorrhage (n = 1), total retinal detachment (n = 1), or pain (n = 1). For 4 preterminal patients, observation was preferred. MAIN OUTCOMES AND MEASURES Clinical features and systemic outcomes. RESULTS The mean interval from primary cancer diagnosis to retinal metastasis was 63 months. Initial misdiagnosis as retinitis (n = 5), hemangioma (n = 1), choroidal neovascular membrane (n = 1), or nerve fiber layer infarction (n = 1) for a mean interval of 5 months was recorded. Visual acuity in the affected eye was 20/40 to 20/60 (n = 5) or 20/400 to light perception (n = 3). The tumors were unilateral (n = 7), involved the macula (n = 3), and had a mean distance to the foveola of 6 mm. In one case, dense vitreous blood precluded fundus visualization. The mean tumor basal dimension was 7.4 mm, and the mean thickness was 2.3 mm. The tumors appeared white (n = 2), yellow (n = 4), or brown (n = 1); were located in the inner retina (n = 6) or full-thickness retina (n = 1); and had vitreous seeds (n = 3), vitreous hemorrhage (n = 2), retinal hemorrhage (n = 4), subretinal fluid (n = 4), and/or intraretinal exudation (n = 1). Fluorescein angiography disclosed early retinal hypofluorescence and late hyperfluorescence with staining. Fine-needle aspiration biopsy confirmed the diagnoses (n = 4). Metastasis-related death occurred in 5 patients within 1 month in each case. Of the remaining 3 patients, 2 were alive at 4 and 17 months and 1 was too sick to return. CONCLUSIONS AND RELEVANCE Retinal metastases resemble retinitis, often with delay in diagnosis and poor life prognosis.

Monocyte chemoattractant protein-1 in the aqueous humour of patients with age-related macular degeneration.

Background:  To investigate the role of inflammation in age‐related macular degeneration by measuring the levels of cytokines in the aqueous humour.

Possible neuroprotective effect of brimonidine in a mouse model of ischaemic optic neuropathy.

Purpose:  To investigate the neuroprotective effect of brimonidine following induction of ischaemic optic neuropathy in rodents (rAION).

Intravitreal bevacizumab as an adjunct treatment for neovascular glaucoma

Purpose To assess the effect of adjunctive intravitreal bevacizumab treatment on neovascular glaucoma (NVG). Methods The medical records of all consecutive patients with NVG treated with intravitreal bevacizumab at our center from May 2006 to February 2008 were reviewed. The data collected included background features, findings on full ophthalmologic examination (including visual acuity, gonioscopy, and intraocular pressure), glaucoma medications prescribed, and additional procedures for glaucoma performed before and after bevacizumab injection. The interval between the diagnosis of NVG and intravitreal bevacizumab treatment was calculated. Results Eighteen patients (6 male, 12 female; mean age 63±13.2 years) met the study criteria. Causes of NVG were proliferative diabetic retinopathy (n=14), central retinal vein occlusion (n=2), occlusive vasculitis (n=1), and panuveitis (n=1). The mean duration of follow-up was 52 (±12) weeks. Mean intraocular pressure decreased from 32.3 (±4.99) to 18 (±6.1) mmHg (p<0.0001) and mean number of glaucoma medications decreased from 3.16 (±1.2) to 2.55 (±1.46) (p=0.1938). An interval of less than 6 months between the start of bevacizumab treatment and diagnosis was associated with better final visual acuity than delayed treatment (0.82±0.4 logMAR vs 1.88±1.1 logMAR, p=0.002) and a better regression of iris neovascularization (22% vs 89%; p=0.015). Conclusions Intravitreal bevacizumab is beneficial for the treatment of anterior segment neovascularization and NVG when used as an adjunct, making the administration of additional treatment for the underlying cause possible. Bevacizumab should be instituted promptly after diagnosis, before irreversible anatomic and functional damage occurs.

Chorioretinectomy for perforating eye injuries

PurposeTo report the outcomes of chorioretinectomy in severe ocular injuries where a foreign body penetrated the choroid or perforated the globe.MethodsThe study sample consisted of a retrospective, non-comparative, consecutive interventional case series of 13 perforating or severe intraocular foreign body ocular injuries that were treated at a single institution from March 2008 to March 2010. All the patients were operated with 20-gauge three-port pars plana vitrectomy (PPV) by removing the choroid and/or retina with scar tissue at the perforation site of the foreign body. The reports of patients were examined for best-corrected visual acuity, globe survival, retinal detachment status, and proliferative vitreoretinopathy.ResultsA total of 13 eyes of 13 patients with a mean age of 25.8±9.0 years (range, 11–38 years) were followed for a median of 13.8±5.4 months (range, 8–29 months). The mean time period between injury and the vitreoretinal surgery was 13.6±9.3 days. All had an exit/impact site wound, eight of which were located in the posterior pole, which caused choroidal and retinal incarceration in the macular area. PPV together with chorioretinectomy, endolaser applications, silicone oil tamponade, with/without encircling band, and lensectomy surgery was applied to all of them. Final best-corrected visual acuity (BCVA) ≥20/200 occurred in 4 of 13 (30.76%) patients. Globe survival rates were 100% (13 of 13), and final retinal attachment rate was 84.6% (11 of 13). The proliferative vitreoretinopathy rate was 2 of 13 (15.3%).ConclusionChorioretinectomy is a surgical option that may decrease post-traumatic proliferative vitreoretinopathy and tractional retinal detachment rates, thus improving final BCVA and increasing globe survival rates when a foreign body penetrates the choroid and perforates the globe.

Sclerochoroidal calcification: clinical features, outcomes, and relationship with hypercalcemia and parathyroid adenoma in 179 eyes.

Purpose: To describe the clinical features and long-term ophthalmic and systemic findings in patients with sclerochoroidal calcification (SCC). Methods: Retrospective non-interventional clinical chart review of 179 eyes of 118 patients with SCC to evaluate for the relationship of SCC with systemic calcium metabolic abnormalities. Results: The mean patient age at diagnosis was 69 years. There were 47 (40%) men and 71 (60%) women of Caucasian (n = 116, 98%) and Hispanic (n = 2, 2%) heritage. The condition was unilateral in 57 patients (48%) and bilateral in 61 (52%), with a mean of 1.6 lesions per eye (range, 1–7 lesions per eye). The referring diagnosis was choroidal nevus (n = 23, 20%), melanoma (n = 15, 13%), lymphoma (n = 12, 10%), metastasis (n = 6, 5%), osteoma (n = 4, 3%), SCC (n = 6, 5%), and no diagnosis (n = 51, 43%). Of 277 SCC lesions, the most common location was superotemporal quadrant (n = 191, 69%). The largest lesion per eye demonstrated mean basal diameter of 3.6 mm and thickness of 1.8 mm, with yellow or white color (n = 150 lesions, 84%) and located superiorly (n = 105, 61%) at the retinal vascular arcade or near the equator (n = 161, 94%). The lesion demonstrated overlying focal choroidal atrophy (n = 63, 35%) and retinal pigment epithelium atrophy (n = 88, 49%). There was no case of subretinal fluid, hemorrhage, or choroidal neovascular membrane. At mean 4 years follow up, there was no lesion enlargement, decalcification, or related subretinal fluid/hemorrhage, choroidal neovascularization, or vision loss. Ocular treatment was not necessary in any case. Systemic outcomes revealed hyperparathyroidism (n = 9/33, 27%) with parathyroid adenoma (n = 5/33, 15%), Bartter syndrome (n = 1/53, 2%), or Gitelman syndrome (n = 6/53, 11%). Conclusions: Sclerochoroidal calcification is a stable deposition of calcium in the sclera that, unlike choroidal osteoma, has minimal risk for vision loss. All patients with SCC should be evaluated for underlying systemic calcium disorders, especially parathyroid and renal metabolic conditions.

Neuroprotective effect of hyperbaric oxygen therapy on anterior ischemic optic neuropathy

The study investigated the therapeutic effect of hyperbaric oxygen (HBO) on anterior ischemic optic neuropathy in a rodent model (rAION). rAION was laser-induced in one eye of 63 mice. The fellow (uninjured) eye served as an internal control. Thirty-three mice underwent two 90-min sessions of 100% oxygen (2 atm) treatment immediately following injury and one session daily thereafter for up to 14 days. The remaining mice were untreated. Retinas were harvested at different time points, and mRNA levels of various genes were analyzed by real-time polymerase chain reaction and histologic study. Untreated mice: day 1 post-rAION – SOD-1 (oxidative-stress-related) decreased to 82% of control (uninjured eye) levels (P < 0.05), Caspase-3 (proapoptotic) decreased to 89%, Bcl-xL mildly increased (117%; all NS); day 3 – HO-1 and endothelial nitric oxide synthase (eNOS; ischaemia-related) decreased to 74%, and Bcl-2-associated X protein, Caspase-3, and B-cell lymphoma 2 (Bcl-2; apoptotic) increased by 170, 120, and 111%, respectively (all NS); day 21 – HO-1 increased to 222% (NS) and eNOS decreased to 48% (P < 0.05). Treated mice: day 1 – SOD-1 and Caspase-3 remained unchanged, Bcl-2 and Bcl-xL mildly increased (112 and 126% respectively); day 3 – HO-1 and eNOS increased, apoptosis-related gene decreased; day 21 – SOD-1 decreased whereas eNOS increased (P < 0.05), and HO-1 increased to a lesser degree than without treatment. None of the oxygen-treated animals had retinal ganglion cell loss or a decrease in Thy-1 expression. In conclusion, HBO treatment after rAION induction influences the expression of apoptosis-related genes as well as oxidative-stress-induced and ischaemia-related genes and may exert a neuroprotective effect.

Interferon Alpha-2a Therapy in Patients with Refractory Behçet Uveitis.

ABSTRACT Purpose: To report the results of IFNα2a therapy in patients with Behçet uveitis refractory to azathioprine-cyclosporine combination treatment. Methods: In a retrospective study, 39 patients treated with either azathioprine-cyclosporine combination treatment (group 1, n = 23) or IFNα2a (group 2, n = 16) with a diagnosis of ocular Behçet disease (BD), were included in the study. Group 2 consisted of patients who did not respond to conventional combination therapy, and were therefore treated with IFNα2a. Clinical response and relapse rates were recorded for each group. Results: The mean number of uveitis attacks/year per patient was 0.8 ± 1.6 in Group 1. In Group 2, a significant decrease in the mean number of uveitis attacks/year per patient was observed after initiation of IFNα2a (2.4 ± 1.8 vs 1.3 ± 2.0) (p<0.05). When the two groups were compared after administration of IFNα2a therapy, no statistical difference was found in terms of uveitis attack/year and attack-free intervals, with a partial response to both treatments. Conclusions: IFNα2a therapy is an effective alternative for Behçet uveitis patients where conventional combination therapy fails.

CLASSIFICATION OF SCLEROCHOROIDAL CALCIFICATION BASED ON ENHANCED DEPTH IMAGING OPTICAL COHERENCE TOMOGRAPHY "MOUNTAIN-LIKE" FEATURES.

Purpose: To describe distinct enhanced depth optical coherence tomography patterns of sclerochoroidal calcification and their correlation to clinical features. Methods: Retrospective chart review of 67 eyes of 46 patients with spectral domain optical coherence tomography imaging. Results: The mean patient age at diagnosis was 68 years. There were 20 (43%) men and 26 (57%) women of white (n = 45, 98%) or Hispanic (n = 1, 2%) heritage. The most prominent sclerochoroidal calcification lesions were located in the superotemporal quadrant (n = 57, 85%) between the temporal arcades and the equator (n = 58, 87%). On enhanced depth optical coherence tomography, the sclerochoroidal calcification was located within the sclera in all cases and the inner surface topography assumed specific “mountain-like” patterns, including flat (Type 1) (n = 9) at median thickness of 1.2 mm, rolling (Type 2) (n = 28) at 1.4 mm thickness, rocky-rolling (Type 3) (n = 21) at 2.1 mm thickness, and table mountain (Type 4) (n = 9) at a thickness of 1.9 mm. The retinal layers were undisturbed in flat lesions, and outer retinal abnormalities were found in all other types. A comparison of the 4 types revealed that Type 3 lesions were thickest (P < 0.001), showing abnormalities in the retinal pigment epithelium, ellipsoid region, and external limiting membrane most commonly (P < 0.05) and demonstrating the most dramatic thinning of the overlying choroid (P < 0.01) and retina (P < 0.05). Type 4 lesions showed greatest basal diameter (P < 0.01) and least outer retinal abnormalities (P < 0.05) or choroid thinning (P < 0.05). Conclusion: In this report, enhanced depth optical coherence tomography has demonstrated that sclerochoroidal calcification is a scleral-based disease and can be classified based on four “mountain-like” topographic patterns, associated with variable effects on the choroid and retina.