ASYMMETRIC DIABETIC RETINOPATHY PROGRESSION IN PATIENTS WITH AXIAL ANISOMETROPIA.

PURPOSE: To investigate the differences in the progression of diabetic retinopathy (DR) in both eyes of patients with axial anisometropia. METHODS: A retrospective review was conducted on diabetic patients who had different axial lengths (difference greater than 1 mm) in each eye. The primary objective of this study was to analyze the differences in the progression of DR in both eyes of patients with axial anisometropia. Fundus images (fluorescein angiography and photographs of the fundus covering the Early Treatment Diabetic Retinopathy Study seven fields) were graded using the Early Treatment Diabetic Retinopathy Study DR grading system. Also, the severity of diabetic retinopathy was analyzed based on the axial length and subfoveal choroidal thickness. RESULTS: Thirty-four of 6,963 patients with DR were included after applying the exclusion and inclusion criteria. The mean age was 53.53 ± 12.20 years and duration of diabetes was 9.63 ± 7.73 years. The mean axial length of the longer and shorter eye was 26.21 ± 2.04 mm and 23.21 ± 1.73 mm, respectively (P < 0.001). In shorter eyes, 61.7% (21 of 34) of the eyes had proliferative diabetic retinopathy. In contrast to the shorter eye, only 8 of the longer eyes (8 of 34, 23.5%) had proliferative diabetic retinopathy (McNemar test, P < 0.001). In eyes with thin subfoveal choroidal thickness (<250 µm), the proliferative diabetic retinopathy ratio was significantly lower (P = 0.007). CONCLUSION: In patients with axial anisometropia, the longer eye had a lower degree of DR progression than the shorter eye. This result showed that elongation of the axial length had a protective effect against the progression of DR without individual confounding factors.

COMPARISON OF VISUAL PROGNOSIS AND CLINICAL FEATURES OF CYTOMEGALOVIRUS RETINITIS IN HIV AND NON-HIV PATIENTS.

PURPOSE: To compare the visual prognosis and clinical features of cytomegalovirus (CMV) retinitis between HIV and non-HIV patients. METHODS: Retrospective cross-sectional study on patients diagnosed with CMV retinitis. Depending on the presence of HIV infection, best-corrected visual acuity (VA) and clinical feature of CMV retinitis were analyzed. The clinical characteristics associated with poor visual prognosis after antiviral treatment were also identified. RESULTS: A total of 78 eyes (58 patients) with CMV retinitis were included in this study: 21 eyes and 57 eyes in HIV and non-HIV patients, respectively. Best-corrected VA was not significantly different between HIV and non-HIV patients. The rate of foveal involvement, retinal detachment, involved zone, and mortality did not significantly differ between the two groups. Visual acuity after antiviral treatment was significantly worse (pretreatment logarithm of the minimal angle of resolution best-corrected VA, 0.54 ± 0.67 [Snellen VA, 20/63]; posttreatment logarithm of the minimal angle of resolution best-corrected VA, 0.77 ± 0.94 [Snellen VA, 20/125]; P = 0.014). Poor visual prognosis was significantly associated with Zone 1 involvement, retinal detachment, and a poor general condition. CONCLUSION: The overall visual prognosis and the clinical features of CMV retinitis do not differ between HIV and non-HIV patients. The visual prognosis of CMV retinitis still remains quite poor despite advancements in antiviral treatment. This poor prognosis after antiviral treatment is associated with retinal detachment during follow-up, Zone 1 involvement, and the poor general condition of the patient.

Pericentral hydroxychloroquine retinopathy in Korean patients.

PURPOSE: A pericentral pattern of hydroxychloroquine (HCQ) retinopathy recently has been recognized in the United States in patients of Asian heritage. We report on an investigation of this pericentral retinopathy within a Korean population. DESIGN: Retrospective, observational study. PARTICIPANTS: Patients taking HCQ who were referred to ophthalmology for screening of HCQ retinopathy. METHODS: The medical records of patients were reviewed, including spectral domain optical coherence tomography, fundus autofluorescence, and visual fields. MAIN OUTCOME MEASURES: Frequency of pericentral pattern of HCQ retinopathy and features of progression. RESULTS: Among 218 patients referred, 9 (4.1%) were diagnosed with toxicity. Of these, 8 had a predominantly pericentral pattern of retinal change, whereas only 1 had the classic parafoveal distribution of retinal damage. Progression of retinopathy was documented in 3 patients followed more than 12 months while taking HCQ. No progression was seen in 2 patients without retinal pigment epithelial (RPE) damage who were followed for at least 12 months after discontinuation of HCQ. CONCLUSIONS: We found that a pericentral pattern of HCQ retinopathy was predominant among Korean patients, rather than the traditional (bull's eye) parafoveal pattern of damage. Retinopathy progressed while on the drug, but the progression stopped in patients with toxicity detected before RPE damage. These observations suggest the need for new approaches when screening for HCQ toxicity in Asian patients.

Postoperative restoration of foveal inner retinal configuration in patients with epiretinal membrane and abnormally thick inner retina.

PURPOSE: To investigate foveal inner retinal layer (IRL) restoration and its relationship with functional visual outcomes after membrane peeling in eyes with idiopathic epiretinal membrane (ERM) with foveal central thick IRL. METHODS: Consecutive eyes (n = 57) with a thick foveal IRL that underwent 25-gauge vitrectomy for ERM treatment were included. Complete ophthalmic and spectral domain optical coherence tomography examinations were performed before and 1 year after surgery. RESULTS: Before surgery, mean best-corrected visual acuity (BCVA) was 20/48 (logMAR, 0.38); central foveal thickness, 515.0 ± 90.9 µm; and central IRL thickness (CIRLT) at the fovea, 167.7 ± 80.1 µm. One year after ERM peeling, mean BCVA improved to 20/30 (logMAR, 0.18), central foveal thickness to 404.1 ± 96.4 µm, and CIRLT to 76.8 ± 68.0 µm. In multivariate analysis, initial BCVA and CIRLT at baseline correlated well with final BCVA and BCVA improvement at 12 months. In comparison with Group B eyes (persistently thick foveal IRL at 12 months), Group A eyes (restored foveal IRL at 12 months) had thinner CIRLT at baseline and showed a significant post-surgical improvement in BCVA and metamorphopsia. CONCLUSION: In eyes with idiopathic ERM and decreased vision due to abnormally thick IRL in the foveal center, postoperative visual outcomes correlated well with preoperative CIRLT and postoperative restoration of IRL configuration after ERM peeling.

SUBFOVEAL CHOROIDAL THICKNESS CHANGES IN TREATED IDIOPATHIC CENTRAL SEROUS CHORIORETINOPATHY AND THEIR ASSOCIATION WITH RECURRENCE.

PURPOSE: To analyze the changes in subfoveal choroidal thickness (SFChT) before and after resolution of central serous chorioretinopathy (CSC) and their association with recurrence during follow-up. METHODS: Seventy-six eyes with CSC that were completely resolved after treatment with either intravitreal bevacizumab (IVB, 42 eyes) or with half-fluence photodynamic therapy (34 eyes) were included. Best-corrected visual acuity and spectral domain optical coherence tomography were performed at baseline, after complete resolution, and at regular intervals thereafter. RESULTS: Subfoveal choroidal thickness was similar in the IVB-treated and half-fluence photodynamic therapy-treated eyes at baseline, as well as after complete resolution of the CSC. However, recurrence was more frequent in the IVB-treated eyes (19.0% vs. 2.9%, P = 0.037). The reduction of SFChT after CSC resolution was greater in the nonrecurrent eyes than in the recurrent eyes (91.35 ± 46.40 vs. 19.25 ± 16.47 µm, P < 0.001), and the extent of SFChT reduction was associated with the rate of recurrence of CSC (odds ratio = 0.877, P = 0.019). When CSC recurred, SFChT increased toward the baseline value. CONCLUSION: Treatment of idiopathic CSC by both IVB and half-fluence photodynamic therapy can reduce SFChT when subretinal fluid is completely resolved. Recurrence is more frequent after IVB and specifically in eyes with a smaller reduction in SFChT after resolution of the CSC.

Recent Clinical Manifestation and Prognosis of Fungal Endophthalmitis: A 7-Year Experience at a Tertiary Referral Center in Korea.

This study analyzed the recent causes, prognosis, and treatment strategies for fungal endophthalmitis. A retrospective review of patients who were diagnosed with fungal endophthalmitis at our center was conducted. The fungal organisms isolated from each patient and the visual prognosis according to the route of infection and treatment method were analyzed. A total of 40 eyes from 30 patients with fungal endophthalmitis were included in this study. Candida species were the most common causative organisms in 35 of 40 eyes. Endogenous and exogenous endophthalmitis were observed in 33 and 7 eyes, respectively. Pre- and post-treatment best-corrected visual acuity (BCVA) was not significantly different between endogenous endophthalmitis and exogenous endophthalmitis. The 40 eyes were treated using the following modalities: intravitreal antifungal agent injection with intravenous antifungal agent (16 eyes), vitrectomy with intravenous antifungal agent (14 eyes), intravenous antifungal agent alone (9 eyes), and evisceration (1 eye). Post-treatment BCVA only significantly improved after treatment in the vitrectomy group. Candida species were the most common cause of fungal endophthalmitis, irrespective of the route of infection. The visual prognosis of fungal endophthalmitis was generally poor. In conclusion, if the general condition of the patient tolerates a surgical procedure, prompt vitrectomy and intravitreal injection of antifungal agents can improve visual acuity.

Effect of combined cataract surgery and ranibizumab injection in postoperative macular edema in nonproliferative diabetic retinopathy.

PURPOSE: To evaluate whether intravitreal ranibizumab injection at cataract surgery prevents postoperative diabetic macular edema (PME) in patients with stable diabetic retinopathy without significant macular edema. METHODS: Eighty patients with cataract, stable diabetic retinopathy, and no significant macular edema were randomized to a sham group (cataract surgery only) or a group undergoing cataract surgery plus intraoperative ranibizumab injection. Best-corrected visual acuities, central subfield thickness, and total macular volume were assessed at baseline and 1 week, 1, 3, and 6 months postoperatively by spectral domain optical coherence tomography. Clinically meaningful PME (central subfield thickness increase >60 µm relative to baseline) was computed. RESULTS: The groups did not differ in baseline best-corrected visual acuity, central subfield thickness, and total macular volume. Compared with the ranibizumab injection group, the sham group had significantly larger central subfield thickness increases relative to baseline at 1 week and 1 month; larger total macular volume increases at all time points (P = 0.012, P = 0.005, P < 0.001, P < 0.001, P = 0.005, P = 0.017, respectively); higher PME frequency at 1 month (P = 0.019); and poorer best-corrected visual acuity improvement from baseline to 6 months after surgery (P = 0.046). CONCLUSION: In patients with stable diabetic retinopathy without significant macular edema, intravitreal ranibizumab injection at cataract surgery may prevent the postoperative worsening of macular edema and may improve the final visual outcome without affecting safety.

Development and progression of diabetic retinopathy and associated risk factors in Korean patients with type 2 diabetes: the experience of a tertiary center.

The aim of this study was to evaluate the incidence of and risk factors for the development of diabetic retinopathy (DR) and progression to proliferative DR (PDR) in Korean patients. Patients diagnosed with type 2 diabetes and followed for more than 5 years at a university-based clinic since 2000 were consecutively enrolled in this retrospective cohort study. Based on the DR classification at the initial and final visits, the incidence and progression of DR was determined and patient characteristics were compared according to DR progression. Hazard ratios of each putative risk factor for DR progression were calculated with a multivariate Cox proportional hazard model. Rate of DR development and progression to PDR were 32.1/1,000 and 26.2/1,000 person-years, respectively. A longer duration of diabetes and higher mean HbA1c level were significant risk factors for the development of DR. Regarding progression to PDR, higher mean HbA1c level, higher standard deviation of HbA1c, and higher urine albumin-to-creatinine ratio were significant risk factors. The rates of development of DR and progression to PDR in Koreans with type 2 diabetes are lower than those reported over the last decade. An inadequate blood glycemic control is the common risk factor for development and progression of DR.

Changes in the clinical features and prognostic factors of endogenous endophthalmitis: fifteen years of clinical experience in Korea.

PURPOSE: To identify changes in the clinical features, management, and prognostic factors of endogenous endophthalmitis in Korea from 1996 through 2010. METHODS: We conducted a retrospective review of medical records of patients diagnosed with endogenous endophthalmitis from January 1996 to December 2010, which was divided into 3 periods: 1996 to 2000, 2001 to 2005, and 2006 to 2010. Variables included age, source of infection, systemic conditions, initial and final visual acuities, causative organisms, and treatment. RESULTS: Endophthalmitis was identified in 80 patients (97 eyes). Diabetes (42.5%) and liver cirrhosis (20%) were the common systemic problems in these patients. Liver abscess (25%) was the most common infection focus of the endophthalmitis. Klebsiella pneumoniae (48.4%) was the common causative agent, although more recently, endophthalmitis caused by gram-positive cocci has increased in frequency. The use of vitrectomy as an initial treatment has increased during the past 5 years. Good initial visual acuity greater than counting fingers (P < 0.001), early vitrectomy in patients with initially good visual presentation (P = 0.035), and gram-positive cocci (P = 0.033) as a causative agent were significantly related to a successful visual outcome. CONCLUSION: Although the prognosis of endogenous endophthalmitis is generally poor in most patients, some eyes can have relatively good visual outcomes if treated appropriately and early enough.

Prevalence and risk factors of early-stage age-related macular degeneration in patients examined at a health promotion center in Korea.

We evaluated the prevalence and risk factors for early age-related macular degeneration (AMD) in Koreans 50 yr of age or older who were examined at a single health promotion center. We retrospectively reviewed the records of 10,449 subjects who visited the center over a 6-month period. Fundus photography was performed on all subjects, and systematic risk factor analysis was conducted using a structured questionnaire. All patients (n = 322) were initially diagnosed with drusen or early AMD using fundoscopy; the control group (n = 10,127) were those yielding normal fundoscopy findings. The age- and gender-adjusted prevalence of early AMD was 3.08%. Advanced age, male gender, smoking status, hyperlipidemia, working outdoors, and residence in rural areas were all significantly associated with an increased risk for development of early AMD. Higher-level ingestion of fruit or herbal medication and an increased amount of exercise were associated with a lower risk of early AMD development. In our Korean cohort, consisting principally of relatively healthy, middle-class urban adults, the prevalence of early AMD was 3.08% that is similar to that reported in earlier epidemiological studies. Several modifiable risk factors such as smoking and hyperlipidemia are associated with the prevalence of early AMD in our cohort.

Recurrent bilateral branch retinal artery occlusion with hearing loss and encephalopathy: the first case report of Susac syndrome in Korea.

We report the first case of Susac syndrome in Koreans, in a 23-yr-old female patient who presented with sudden visual loss and associated neurological symptoms. Ophthalmic examination and fluorescein angiography showed multiple areas of branch retinal artery occlusion, which tended to recur in both eyes. Magnetic resonance imaging showed dot-like, diffusion-restricted lesions in the corpus callosum and left fornix, and audiometry showed low-frequency sensory hearing loss, compatible with Susac syndrome. She received immunosuppressive therapy with oral steroid and azathioprine. Three months later all the symptoms disappeared but obstructive vasculitis have been relapsing. This patient demonstrated the entire clinical triad of Susac syndrome, which tends to occur in young females. Although this disorder has rarely been reported in Asian populations, a high index of suspicion is warranted for early diagnosis and timely treatment.

Clinical feature and visual prognosis of acute retinal necrosis according to the initially involved zone and extent: 10-year experience.

PURPOSE:: We aimed to analyze the visual prognosis and clinical characteristics of acute retinal necrosis according to the initially involved zone and extent. STUDY DESIGN:: Retrospective, consecutive, cross-sectional study. METHODS:: We retrospectively reviewed acute retinal necrosis patients who were treated with systemic antiviral treatment, and assessed the visual prognosis of acute retinal necrosis following antiviral treatment based on the initially involved zone and the extent of acute retinal necrosis at the time of diagnosis. Moreover, we evaluated whether prophylactic laser photocoagulation had preventive effects on retinal detachment. RESULTS:: A total of 43 eyes from 35 patients with acute retinal necrosis were included. Eyes with zone I involvement/extensive retinal lesions showed poor visual prognosis (logMAR: 1.17 ± 0.97 vs 0.49 ± 0.81; p = 0.014) and a higher incidence of retinal detachment (9/30 (30.0%) vs 0/13 (0%); p = 0.039) after treatment. Retinal detachment was observed in 20.9% of cases, and its incidence was significantly lower in eyes that had undergone prophylactic laser photocoagulation. CONCLUSION:: The overall visual prognosis of acute retinal necrosis is poor and can be determined at the time of diagnosis. Prophylactic laser photocoagulation exhibits preventive effects with regard to the development of retinal detachment. Therefore, laser photocoagulation should be actively considered in eyes with extensive retinal lesions to prevent retinal detachment and thus eventually improve the overall visual prognosis of acute retinal necrosis.

Optical coherence tomography evaluation of detached macula from rhegmatogenous retinal detachment and central serous chorioretinopathy.

PURPOSE: To compare structural changes using optical coherence tomography (OCT) and visual acuity (VA) loss in patients with shallow macula-off rhegmatogenous retinal detachment (RD) and central serous chorioretinopathy (CSC) involving the macula. DESIGN: Retrospective, comparative observational study. METHODS: Fifteen eyes with rhegmatogenous RD and 21 eyes with CSC with comparable height of macular detachment (< or = 550 microm) were evaluated retrospectively. All eyes were subjected to complete ophthalmologic examination, including OCT analysis, and were followed up until complete resolution of RD. RESULTS: The mean height +/- standard deviation at the fovea was 290 +/- 153 microm in rhegmatogenous RD and 310 +/- 141 microm in CSC. Although the duration of symptoms was longer in CSC than in rhegmatogenous RD (35.0 +/- 38.0 days vs 8.3 +/- 8.0 days), initial (0.25 vs 0.64 logarithm of the minimum angle of resolution [logMAR] units; P = .001) and final VA (0.09 vs 0.49 logMAR units; P < .001) were significantly better in CSC. OCT analysis of rhegmatogenous RD showed intraretinal cyst formation, intraretinal separation, and undulation of outer detached retina in 10 (67%), nine (60%), and six (40%) eyes, respectively. Eyes with two or more preoperative structural changes had poorer initial VA than eyes with none or one structural change. In comparison, none of the 21 CSC eyes showed any of these changes (P < .001). CONCLUSIONS: Compared with CSC, macula-involving rhegmatogenous RD resulted in more rapid visual loss, despite similar height of foveal detachment. Structural changes on OCT may be correlated with different levels of visual function in these two conditions.

The therapeutic effects of bevacizumab in patients with polypoidal choroidal vasculopathy.

PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab for polypoidal choroidal vasculopathy (PCV). METHODS: In this retrospective interventional pilot study, 12 eyes of 11 patients with active PCV were treated with intravitreal bevacizumab (1.25 mg) alone or in combination with photodynamic therapy (PDT) depending on the informed patient's choice. Intravitreal bevacizumab was repeated at 6-week intervals until the regression of active lesion was detected on fluorescein angiography (FA) which was done on a regular basis, Indocyanine green angiography (ICGA) and optical coherence tomography (OCT) analyses. RESULTS: Intravitreal bevacizumab was given alone in 8 eyes (Group 1) and in combination with PDT in 4 eyes (Group 2). Mean follow-up duration was 17 weeks in group 1 and 15 weeks in group 2 after bevacizumab treatment. The mean number of bevacizumab injections was 2.2 in group 1 and 2.5 in group 2. Mean BCVA improved from 20/63 to 20/40 in group 1 and 20/63 to 20/32 in group 2. Of all eyes, the BCVA improved by > or = 2 lines in seven (58%) eyes and resolution of fluid and hemorrhages in clinical examination, an absence of leakage on repeat FAs, or resolved pigment epithelial detachment (PED) and/or subretinal fluid (SRF) on OCT exam was confirmed in 10 (83%) eyes. Partial or complete regression of the polypoidal vessels and interconnecting vessels was reported for most cases at the last follow-up. No significant ocular or systemic side effects were observed in both groups. CONCLUSIONS: Short-term results indicate that intravitreal bevacizumab (1.25 mg) alone or in combination with PDT is well tolerated and associated with improvement in BCVA and reduced angiographic leakage in most patients. Further evaluation of intravitreal bevacizumab therapy for the treatment of PCV is warranted.

Subconjunctival Injection of Viscoelastic Material for Leaking Sclerotomy in Transconjunctival Sutureless Vitrectomy.

Aim. To evaluate the effectiveness of subconjunctivally injected viscoelastic material (VEM) for the self-sealing of leaking sclerotomy in transconjunctival sutureless vitrectomy (TSV). Methods. This was a prospective interventional series. Subconjunctival injection of VEM was performed in eyes showing leaking sclerotomy at the end of TSV in selected cases. This procedure was performed in 24 consecutive eyes from 24 patients scheduled for 23- or 25-gauge TSV with phacoemulsification for various vitreoretinal diseases combined with cataracts. Results. Among the 24 eyes, 13 cases were scheduled for 23-gauge TSV, while 11 cases were scheduled for 25-gauge TSV. The average number of injection sites per eye was 1.7 ± 0.9 in the 23-gauge cases and 1.5 ± 0.7 in the 25-gauge cases. Leakage was most commonly observed at the vitrector site of the sclerotomy, while little leakage was observed at the illuminator site. There were no cases of postoperative hypotony. Conclusion. Subconjunctival injection of VEM was simple and effective for the self-sealing of leaking sclerotomy after TSV in selected cases.

Effect of Posterior Subtenon Triamcinolone Acetonide Injection on Diabetic Macular Edema Refractory to Intravitreal Bevacizumab Injection.

PURPOSE: To evaluate the effects of posterior subtenon triamcinolone acetonide injection on refractory diabetic macular edema (DME) after intravitreal bevacizumab (IVB) injection failure. METHODS: Patients with DME and central subfield thickness (CST) >300 µm who did not respond to IVB injections were retrospectively included. Specifically, we enrolled patients who were diagnosed with refractory DME and who experienced an increase in CST after 1 to 2 IVB injections or no decrease after ≥3 consecutive IVB injections. One clinician injected 20 mg of triamcinolone acetonide into the posterior subtenon space. All patients received ophthalmic examinations at baseline and at 2, 4, and 6 months post-baseline. Examinations included Snellen visual acuity, intraocular pressure, and spectral-domain optical coherence tomography. RESULTS: Forty eyes of 34 patients were included. The average baseline CST was 476 µm. The average CST decreased to 368 µm at 2 months, 374 µm at 4 months, and 427 µm at 6 months (p < 0.001 for all results, Wilcoxon signed-rank test). The average intraocular pressure increased from 15.50 to 16.92 mmHg at 2 months but decreased to 16.30 mmHg at 4 months and 15.65 mmHg at 6 months. Logarithm of the minimum angle of resolution visual acuity improved from 0.56 to 0.50 at 2 months (p = 0.023), 0.50 at 4 months (p = 0.083), and 0.48 at 6 months (p = 0.133, Wilcoxon signed-rank test). No complications were detected. CONCLUSIONS: Posterior subtenon triamcinolone acetonide is an effective and safe treatment for reducing CST in DME refractory to IVB.

Choroidal Thickness in Eyes with Unilateral Ocular Ischemic Syndrome.

Aim. To analyze the subfoveal choroid thickness and choroidal volume in unilateral ocular ischemic syndrome (OIS). Methods. A retrospective review was conducted for all patients with unilateral OIS from October 2010 through June 2014. The subfoveal choroidal thickness (SFChT) and choroidal volume of both eyes were compared. Results. 19 unilateral OIS patients were included in this study. The mean SFChT of OIS eyes was significantly lower than that of fellow eyes (OIS eyes: 208.89 ± 82.62 µm and fellow eyes: 265.31 ± 82.77 µm, P < 0.001). The choroidal volume of OIS eyes was significantly smaller than that of fellow eyes (OIS eyes: 0.16 ± 0.05 mm(3) and fellow eyes: 0.21 ± 0.05 mm(3), P < 0.001). Conclusion. The choroidal thickness and volume of OIS eyes were smaller than those of unaffected fellow eyes. Decreased choroidal circulation caused by carotid artery stenosis might affect the discordance of choroidal thickness and choroidal volume.

Anti-angiogenic effect of metformin in mouse oxygen-induced retinopathy is mediated by reducing levels of the vascular endothelial growth factor receptor Flk-1.

PURPOSE: To evaluate the effect of metformin on vascular changes in oxygen-induced retinopathy (OIR) in mouse, and to elucidate the possible underlying mechanism. METHODS: OIR mice were treated with metformin by intraperitoneal injection from postnatal day 12 (P12) to P17 or P21. At P17 and P21, vessel formation and avascular areas were assessed using retinal flat mounts. Levels of vascular endothelial growth factor (VEGF) were measured by enzyme-linked immunosorbent assays, and the effects of metformin on VEGF-induced proliferation of human umbilical vein endothelial cells (HUVECs) were assessed. The effects of metformin on the levels of Flk1 (VEGF receptor-2) and phosphorylated Flk1 (pFlk1) were measured by Western blotting (HUVECs) and immunohistochemistry (retinal tissue). RESULTS: Retinal morphologic changes were analyzed between two groups (saline-treated OIR; metformin-treated OIR). Metformin treatment did not change the extent of avascular areas at P17. However, at P21, when OIR pathology was markedly improved in the saline-treated group, OIR pathology still remained in the metformin-treated OIR group. VEGF expression levels did not differ between metformin- and saline-treated OIR groups at P17 and P21, but Flk1 levels were significantly reduced in the metformin group compared with saline-treated OIR group. Moreover, metformin inhibited VEGF-induced cell proliferation and decreased levels of Flk1 and pFlk1, consistent with the interpretation that metformin inhibits vascular growth by reducing Flk1 levels. CONCLUSION: Metformin exerts anti-angiogenesis effects and delays the normal vessel formation in the recovery phase of OIR in mice, likely by suppressing the levels of Flk1.