Autocrine CCL2, CXCL4, CXCL9 and CXCL10 signal in retinal endothelial cells and are enhanced in diabetic retinopathy.

This study aimed at examining the presence and role of chemokines (angiogenic CCL2/MCP-1 and angiostatic CXCL4/PF-4, CXCL9/Mig, CXCL10/IP-10) in proliferative diabetic retinopathy (PDR). Regulated chemokine production in human retinal microvascular cells (HRMEC) and chemokine levels in vitreous samples from 40 PDR and 29 non-diabetic patients were analyzed. MCP-1, PF-4, Mig, IP-10 and VEGF levels in vitreous fluid from PDR patients were significantly higher than in controls. Except for IP-10, cytokine levels were significantly higher in PDR with active neovascularization and PDR without traction retinal detachment (TRD) than those in inactive PDR, PDR with TRD and control subjects. Exploratory regression analysis identified associations between higher levels of IP-10 and inactive PDR and PDR with TRD. VEGF levels correlated positively with MCP-1 and IP-10. Significant positive correlations were observed between MCP-1 and IP-10 levels. In line with these clinical findings Western blot analysis revealed increased PF-4 expression in diabetic rat retinas. HRMEC produced MCP-1, Mig and IP-10 after stimulation with IFN-γ, IL-1ß or lipopolysaccharide. IFN-γ synergistically enhanced Mig and IP-10 production in response to IL-1ß or lipopolysaccharide. MCP-1 was produced by HRMEC in response to VEGF treatment and activated HRMEC via the ERK and Akt/PKB pathway. On the other hand, phosphorylation of ERK induced by VEGF and MCP-1 was inhibited by PF-4, Mig and IP-10. In accordance with inhibition of angiogenic signal transduction pathways, PF-4 inhibited in vitro migration of HRMEC. Thus, regulatory roles for chemokines in PDR were demonstrated. In particular, IP-10 might be associated with the resolution of active PDR and the development of TRD.

Prognostic factors after primary vitrectomy and perfluorocarbon liquids for bullous rhegmatogenous retinal detachment.

PURPOSE: To identify prognostic factors for visual acuity and anatomic outcomes associated with bullous rhegmatogenous retinal detachment (RRD) management using primary pars plana vitrectomy, intraoperative perfluorocarbon liquids (PFCLs), and internal gas tamponade. METHODS: The authors studied a consecutive series of 115 eyes (115 patients) with a bullous RRD not complicated by proliferative vitreoretinopathy (PVR) associated with large, multiple, and/or posterior breaks in 58 (50.4%) eyes. All eyes underwent vitrectomy, injection of PFCL, and gas tamponade as the primary procedure. Encircling scleral bands were placed in all cases. The follow-up period ranged from 3 to 60 months (mean 16.6+/-14.1 months). RESULTS: Retinal reattachment was achieved in 92.2% of eyes (106/115) with one operation and in all eyes after a second procedure. PVR was observed in 1 (0.87%) eye and preretinal membranes in 3 (2.6%) eyes. Progression of pre-existing cataract and development of new cataract occurred in 45 (58.4%) of the 77 phakic eyes. The presence of inferior retinal breaks was significantly associated with redetachment after the first procedure (p=0.0156). On univariate analysis, better preoperative visual acuity (p<0.001), macular sparing retinal detachment (p<0.001), and fewer quadrants involved by the detachment (p=0.0015) were significant positive prognostic factors for final visual acuity. Logistic regression analysis highlighted that macular sparing retinal detachment and absence of trauma were associated with better final visual acuity. CONCLUSIONS: Redetachment was associated with the presence of inferior retinal breaks. Visual recovery was dependent on preoperative visual acuity, macular involvement, extent of retinal detachment, and trauma.

Uveitis survey in children.

BACKGROUND/AIMS: This is a retrospective cohort uveitis survey to determine the clinical features of uveitis in children and assess the rate of complications at two referral centres in Saudi Arabia. METHODS: All children under the age of 16 years presenting with uveitis for the first time between 1997 and 2007 to The Eye Center and King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia were included. Clinical features of uveitis entities were described. Last follow-up visual acuity and ocular complications were analysed. RESULTS: A total of 163 cases of uveitis in children were included. The age range was 1-16 years with a mean age of 10 years. The most frequent clinical type of uveitis in children included acute anterior non-granulomatous uveitis 26%, intermediate uveitis 20%, Vogt-Koyanagi-Harada (VKH) disease 16% and juvenile idiopathic arthritis (JIA) 15%. Anterior uveitis accounted for 42%, intermediate for 20%, posterior for 7%, and panuveitis for 31%. Immune-mediated uveitis was present in 144 (88%) patients, while infectious causes manifested in 19 (12%) patients. CONCLUSIONS: The most common cause of uveitis in children was anterior non-granulomatous uveitis of undetermined aetiology. There was a high prevalence of intermediate uveitis, VKH and JIA. Infectious causes of uveitis were uncommon.

Full preoperative panretinal photocoagulation improves the outcome of trabeculectomy with mitomycin C for neovascular glaucoma.

PURPOSE: To investigate the efficacy of full panretinal photocoagulation (PRP) followed by trabeculectomy with mitomycin C (MMC) in the management of eyes with neovascular glaucoma (NVG). METHODS: This study is based on 30 consecutive eyes of 27 patients with NVG who underwent full PRP followed by trabeculectomy with MMC. NVG was secondary to proliferative diabetic retinopathy (23 eyes) and central retinal vein occlusion (7 eyes). Kaplan-Meier survival analysis of the surgical outcome was performed. Operative success was defined as an intraocular pressure (IOP) of < or = 21 mmHg without medical therapy. RESULTS: Kaplan-Meier cumulative success rates at the 6-, 12-, and 24-month intervals were 86.5%, 74.7%, and 57.6%, respectively. Pseudophakia was the only identified significant risk factor for failure (p=0.0138; Fisher exact test). Additional surgical procedures were performed in 8 (26.6%) eyes. The mean IOP decreased from 41.0+/-10.2 mmHg to 18.2+/-9.2 mmHg (p<0.001; Wilcoxon signed rank test). The number of anti-glaucoma medications was reduced from 3.1+/-0.5 preoperatively to 0.3+/-0.7 postoperatively (p<0.001; Wilcoxon signedrank test). Twenty-four (80%) eyes were classified as surgical success after a mean followup period of 17.3+/-22.1 months. Twenty-two (73.3%) eyes had improved vision or retained preoperative vision. CONCLUSIONS: Full PRP followed by trabeculectomy with MMC can effectively reduce the elevatedIOP associated with NVG. Presence of pseudophakia is a significant negative predictor of surgical outcome.

Circulating fibrocytes contribute to the myofibroblast population in proliferative vitreoretinopathy epiretinal membranes.

BACKGROUND/AIMS: Fibrocytes, circulating cells that co-express markers of haematopoietic stem cells, leucocytes and fibroblast products, traffic to sites of tissue injury, differentiate into myofibroblasts and contribute to wound healing and fibrosis. We investigated the presence of fibrocytes and the expression of their chemotactic pathways CCL21/CCR7 and CXCL12/CXCR4 in proliferative vitreoretinopathy (PVR) epiretinal membranes. METHODS: Sixteen membranes were studied by immunohistochemical techniques. RESULTS: Cells expressing alpha-smooth-muscle actin (alpha-SMA), a marker of differentiation of fibrocytes into myofibroblasts, were present in all membranes. Cells expressing the haematopoietic stem-cell antigen CD34, the leucocyte common antigen CD45, CCR7, CXCR4, CCL21 and CXCL12 were noted in 50%, 75%, 68.8%, 100%, 80% and 93.8% of the membranes, respectively. Double immunohistochemistry indicated that all cells expressing CD34, CD45, CCR7, CXCR4, CCL21 and CXCL12 co-expressed alpha-SMA. The number of cells expressing CD34 correlated significantly with the numbers of cells expressing CXCL12 (r(s) = 0.567; p = 0.022) and CCL21 (r(s) = 0.534; p = 0.04). CONCLUSIONS: Circulating fibrocytes may function as precursors of myofibroblasts in PVR membranes.

Prognostic factors associated with outcomes after giant retinal tear management using perfluorocarbon liquids.

PURPOSE: To identify prognostic factors for visual acuity and anatomic outcomes associated with giant retinal tear management using intraoperative perfluorocarbon liquids. METHODS: All patients with giant retinal tears without proliferative vitreoretinopathy (PVR) who underwent management with intraoperative perfluorocarbon liquids between 1994 and 2005 were reviewed. RESULTS: The study included 115 patients (117 eyes), 93 (80.9%) males and 22 (19.1%) females, with a mean age of 30.3+/-15.2 years. Mean follow-up period was 29.7+/-26.7 months. Success rate with primary procedure was 78.6%, which increased to 94% with multiple surgeries. On univariate analysis, factors significantly associated with final visual acuity better than 20/200 included phakic/clear lens at presentation (p=0.0113), partial retinal detachment (p=0.0233), absence of all postoperative complications (p=0.0122), absence of recurrent retinal detachment (p=0.0406), and absence of postoperative PVR (p=0.0062). Logistic regression analysis highlighted that phakic/clear lens at presentation, unfolded flap of the giant tear, absence of postoperative cataract, and absence of postoperative PVR were associated with final visual acuity better than 20/200. On univariate analysis, use of gas tamponade was significantly associated with recurrent retinal detachment (p=0.0190). Logistic regression analysis highlighted that placement of an encircling scleral buckle and use of silicone oil tamponade were associated with anatomic reattachment with primary procedure. CONCLUSIONS: Encircling scleral buckling and silicone oil tamponade decrease the risk of recurrent retinal detachment.

Vogt-Koyanagi-Harada disease in children.

PURPOSE: To identify prognostic factors for outcome in children with Vogt-Koyanagi-Harada (VKH) disease. METHODS: All children 16 years and younger with acute uveitis associated with VKH disease treated between 1999 and 2006 were reviewed. RESULTS: Twenty-three children (46 eyes) were identified; 20 (87%) girls and three (13%) boys with a mean age at presentation of 12.5+/-2.4 years. Mean follow-up period was 48.6+/-30.8 months. Visual acuity of 20/40 or better was achieved in 38 (82.6%) eyes. Eleven eyes developed at least one complication, including cataract in eight eyes, glaucoma in eight eyes, subretinal neovascular membranes in two eyes, and subretinal fibrosis in one eye. Disease recurred during follow-up in 18 eyes. Development of complications was negatively associated with final visual acuity of 20/20 (P=0.0317). Shorter interval between symptoms and treatment was a predictor of final visual acuity of 20/20 (odds ratio=10.4; 95% confidence interval=1.61-67.3). Recurrence of inflammation was significantly associated with development of complications (P=0.003), worse visual acuity (P=0.022) and presence of posterior synechiae of the iris at presentation (P=0.0083), longer interval between symptoms and treatment (P=0.013), initial treatment with intravenous corticosteroids (P=0.0012), and rapid tapering of corticosteroids (P=0.0063). CONCLUSION: Visual prognosis of VKH in children is generally favourable. Clinical findings at presentation, development of complications, interval between symptoms and treatment, recurrence of inflammation, use of intravenous corticosteroids, and method of tapering of systemic corticosteroids were significant prognostic factors.

Expression of chemokines and gelatinase B in sympathetic ophthalmia.

PURPOSE: To examine the expression of gelatinase B (matrix metalloproteinase-9) and the chemokines monocyte chemotactic protein-1 (CCL2/MCP-1) and stromal cell-derived factor-1 (CXCL12/SDF-1) in sympathetic ophthalmia (SO). METHODS: Five enucleated exciting eyes with a clinical diagnosis and typical histopathological findings of SO were studied by immunohistochemical techniques using a panel of monoclonal antibodies directed against gelatinase B, MCP-1, and SDF-1. In addition, a panel of monoclonal and polyclonal antibodies was used to characterize the composition of the inflammatory infiltrate. RESULTS: In all cases, the extensive uveal inflammatory infiltrate was organized as a diffuse infiltrate and as large granulomas consisting of epithelioid cells and multinucleated giant cells. CD20(+) B lymphocytes predominated in the diffuse infiltrate and CD3(+) T lymphocytes were few. The monocyte/macrophage marker CD68 was expressed in scattered inflammatory mononuclear cells and within granulomas and Dalen-Fuchs nodules. Most of the inflammatory cells were HLA-DR(+). Immunoreactivity for gelatinase B, MCP-1, and SDF-1 was observed in cells within granulomas and in scattered epithelioid cells. Immunoreactivity for MCP-1 was noted in retinal pigment epithelial cells. Endothelial cells of choriocapillaries showed weak immunoreactivity for SDF-1. CONCLUSIONS: Gelatinase B, MCP-1, and SDF-1 might have a pathogenic role in the recruitment of leucocytes into the eye in SO.

Expression of antiapoptotic and proapoptotic molecules in diabetic retinas.

PURPOSE: To investigate the expression of the antiapoptotic and proapoptotic markers in diabetic retinas. METHODS: In total, 12 donor eyes from six subjects with diabetes mellitus, and 10 eyes from five nondiabetic subjects without known ocular disease serving as control subjects were examined. Immunohistochemical techniques were used with antibodies directed against cyclooxygenase-2 (Cox-2), Akt (protein kinase B), Mcl-1, Bad, cytochrome c, apoptosis-inducing factor (AIF), tumour necrosis factor receptor-1-associated death domain protein (TRADD), and Fas-associated death domain protein (FADD). RESULTS: In retinas from all subjects without diabetes, cytoplasmic immunoreactivity for the antiapoptotic molecules Cox-2, Akt, and Mcl-1 was noted in ganglion cells. Cytoplasmic immunostaining for Cox-2 was also noted in the retinal pigment epithelial cells. Weak immunoreactivity for the mitochondrial apoptogenic proteins cytochrome c, and AIF was noted in the inner segments of photoreceptors, in the inner one-third of the outer plexiform layer, in cells in the inner nuclear layer, in the inner plexiform layer, and in ganglion cells. There was no immunoreactivity for the other antibodies tested. All diabetic retinas showed de novocytoplasmic immunoreactivity for Bad in ganglion cells, and in occasional cells in the inner nuclear layer. Upregulation of cytochrome cand AIF immunoreactivity was noted. Cox-2, Akt, and Mcl-1 immunoreactivity was not altered in the diabetic retinas. There was no immunoreactivity for TRADD, and FADD. CONCLUSIONS: Ganglion cells in diabetic and nondiabetic retinas express the antiapoptotic molecules Cox-2, Akt, and Mcl-1. Retinal ganglion cells express the proapoptotic molecule Bad in response to diabetes-induced neuronal injury. Diabetic retinas show upregulation of the mitochondrial proteins cytochrome c, and AIF.

Sympathetic ophthalmia after successful retinal reattachment surgery with vitrectomy.

PURPOSE: To report a case of sympathetic ophthalmia (SO) following one successful pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment. METHODS: Case report. RESULTS: A 50-year-old man developed SO 5 weeks after successful repair of rhegmatogenous retinal detachment with PPV and intraocular gas tamponade. The patient presented with bilateral multifocal exudative retinal detachments and inflamed optic nerve with characteristic changes of SO detected by fluorescein angiography, indocyanine green angiography, and optical coherence tomography. Prompt use of systemic steroids and cyclosporin A resulted in control of the uveitis with significant visual improvement. CONCLUSIONS: PPV should be viewed as a major risk factor for development of SO.

Immunopathogenesis of conjunctival remodelling in vernal keratoconjunctivitis.

PURPOSE: To study the processes involved in mediating conjunctival remodelling in vernal keratoconjunctivitis (VKC) by investigating the expression of integrin receptors, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), transforming growth factor-beta(TGF-beta), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and Ki67 antigen, which is a marker for cell proliferation. METHODS: Conjunctival biopsy specimens from 16 patients with active VKC and nine control subjects were studied by immunohistochemical techniques using monoclonal and polyclonal antibodies directed against the integrin alpha3 and alpha6 subunits, EGFR, VEGF, TGF-beta, bFGF, PDGF, and Ki67 antigen. The phenotype of inflammatory cells expressing growth factors was examined by double immunohistochemistry. RESULTS: In the normal conjunctiva, very weak immunoreactivity was observed for EGFR and VEGF in epithelial cells, and for alpha3 and alpha6 integrin subunits on basal epithelial cells, and on vascular endothelial cells in the upper substantia propria. There was no immunoreactivity for the other antibodies. In VKC specimens, strong staining for alpha3 and alpha6 integrin subunits was observed on the membranes of basal and suprabasal epithelial cells, and all vascular endothelial cells. Immunoreactivity for Ki67 antigen was observed in the nuclei of the basal and suprabasal epithelial cells. Strong immunoreactivity was observed for EGFR in the deeper layers of the epithelium, and for VEGF in all epithelial cells. Inflammatory cells expressing EGFR, VEGF, TGF-beta, bFGF, and PDGF were noted in 8, 9, 11, 10, and 10 specimens, respectively. The majority of inflammatory cells expressing growth factors were eosinophils (45+/-4%) and monocytes/macrophages (35+/-4%). CONCLUSIONS: Chronic conjunctival inflammation in VKC is associated with increased staining of alpha3, and alpha6 integrin subunits, EGFR, VEGF, TGF-beta, bFGF, and PDGF that might mediate conjunctival remodelling.

Expression of growth factors in the conjunctiva from patients with active trachoma.

PURPOSE: The blinding complications of trachoma are associated with progressive conjunctival fibrosis due to excessive accumulation of extracellular matrix (ECM) components. We studied the processes involved in the regulation of fibrosis in trachoma by investigating the expression of the fibrogenic and angiogenic connective tissue growth factor (CTGF) and basic fibroblast growth factor (bFGF), the angiogenic vascular endothelial growth factor (VEGF), the angiogenesis-associated endothelial cell marker CD105 (endoglin), and the ECM protein tenascin in the conjunctiva. METHODS: Conjunctival biopsy specimens from six patients with active trachoma, and six control subjects were studied by immunohistochemical techniques using monoclonal and polyclonal antibodies directed against CTGF, bFGF, VEGF, CD105, and tenascin. RESULTS: In the normal conjunctiva, weak immunoreactivity for VEGF was observed in epithelial cells. There was no immunoreactivity for the other antibodies. In all trachoma specimens, immunoreactivity for CTGF and bFGF was localized in monocytes/macrophages, positive for the CD68 marker. Strong immunoreactivity for VEGF was observed in epithelial cells and on vascular endothelial cells. CD105 immunoreactivity was observed on vascular endothelial cells. Immunoreactivity for tenascin was noted in the upper substantia propria. CONCLUSIONS: These findings suggest that macrophages play an active role in conjunctival scarring, upregulated local production of CTGF, bFGF, and VEGF contributes to both fibrous tissue growth and angiogenesis, vascular endothelial cells are activated and are undergoing active angiogenesis, and deposition of tenascin reflect remodelling of the conjunctiva in trachomatous conjunctivitis.

Inducible nitric oxide synthase and vascular endothelial growth factor are colocalized in the retinas of human subjects with diabetes.

PURPOSE: Nitric oxide (NO) mediates vascular endothelial growth factor (VEGF)-induced angiogenesis and vascular hyperpermeability. This study was undertaken to study the cellular distribution of inducible nitric oxide synthase (iNOS) and VEGF in the retinas from human subjects with diabetes mellitus. In addition, glial reactivity and peroxynitrite generation were detected by immunolocalization of glial fibrillary acidic protein (GFAP) and nitrotyrosine, respectively. METHODS: Eight post-mortem eyes from four consecutive subjects with diabetes mellitus and eight eyes from four subjects without diabetes and without known ocular disease were prospectively collected and examined. We used immunohistochemical techniques and antibodies directed against iNOS, VEGF, GFAP, and nitrotyrosine. RESULTS: In retinas from all subjects without diabetes, weak GFAP immunoreactivity was confined to nerve fibre and ganglion cell layers. There was no immunoreactivity for iNOS, nitrotyrosine, and VEGF. All diabetic retinas showed GFAP induction in Müller cells and GFAP upregulation in nerve fibre and ganglion cell layers. All diabetic retinas showed cytoplasmic immunoreactivity for iNOS, and VEGF in ganglion cells, cells in the inner nuclear layer, and glial cells. In serial sections, ganglion cells and cells in the inner nuclear layer expressing VEGF were localized in the same area of iNOS-expressing ganglion cells and cells in the inner nuclear layer. Six retinas from three subjects with diabetes showed immunoreactivity for nitrotyrosine in vascular endothelial cells in inner retinal layer. CONCLUSIONS: iNOS and VEGF are colocalized in diabetic retinas. Increased GFAP immunoreactivity is a pathological event in the retina during diabetes.

Late onset posttraumatic Propionibacterium acnes endophthalmitis.

PURPOSE: To report a case of late onset posttraumatic endophthalmitis secondary to Propionibacterium acnes infection. METHODS: Interventional case report. RESULTS: A 28-year-old man developed endophthalmitis 6 months after a penetrating trauma. The patient underwent pars plana lensectomy and vitrectomy along with injection of intravitreal antibiotics. Anaerobic cultures of the vitreous yielded P. acnes. Seven months after surgery, the eye was quiet with a best-corrected visual acuity of 20/60. CONCLUSIONS: This case emphasizes the importance of considering P. acnes when treating patients with late onset posttraumatic endophthalmitis. (Eur J Ophthalmol 2004; 14: 442-4).

Immuno-histochemical evaluation of conjunctival remodelling in vernal keratoconjunctivitis.

PURPOSE: To study the expression of the extracellular matrix (ECM) proteins, tenascin, laminin, and fibronectin in the conjunctiva of patients with active vernal keratoconjunctivitis (VKC). METHODS: Conjunctival biopsy specimens were obtained from nine patients with active VKC and 6 normal control subjects. The presence and distribution of tenascin, laminin, and fibronectin were assessed microscopically with immunohistochemical techniques and a panel of monoclonal and polyclonal antibodies directed against tenascin, laminin, and fibronectin. RESULTS: In normal conjunctiva, weak immunoreactivity for tenascin was localized to the walls of blood vessels in the upper substantia propria. Weak immunoreactivity for laminin was located at the epithelial-stromal junction and in the walls of blood vessels. Staining for fibronectin was absent. In VKC specimens, intense immunoreactivity for tenascin was noted in the substantia propria associated with the inflammatory infiltrate and in the perivascular stroma. Intense immunoreactivity for laminin around all stromal vessels and fibrillar immunoreactivity among basal epithelial cells were noted. There was no immunoreactivity for fibronectin. CONCLUSION: Our data indicate increased deposition of tenascin and laminin in the conjunctiva from patients with active VKC. Our findings suggest that tenascin and laminin might play distinct roles in chronic inflammation seen in VKC.

Outcome of temporary silicone oil tamponade in complex rhegmatogenous retinal detachment.

PURPOSE: To evaluate the anatomic and visual outcomes and complications of temporary silicone oil (SO) retinal tamponade in patients with complex rhegmatogenous retinal detachments (RD). METHODS: The retrospective study included 100 eyes of 93 consecutive patients. Indications for the use of SO were proliferative vitreoretinopathy (PVR) (30 eyes), difficult RD (30 eyes), giant retinal tears (17 eyes), RD after penetrating trauma (14 eyes), and macular holes in highly myopic eyes (9 eyes). Vitrectomy surgery was performed with 5000-centistoke SO as the retinal tamponade. All eyes underwent prophylactic 360 degree retinopexy at the time of the retinal reattachment operation. The mean duration of SO tamponade was 26.4 weeks, with a mean follow-up of 67.5 weeks after removal of SO. RESULTS: . In 6 of 100 eyes (6%), the retina redetached after removal of SO. Including the successfully reoperated eyes, the final anatomic success rate was 96%. Other complications were cataract (61%), increased intraocular pressure (13%), hypotony (4%), keratopathy (4%), intravitreal hemorrhage (1%), and suprachoroidal hemorrhage (1%). Correspondence analysis demonstrated that redetachment and hypotony were associated with PVR and trauma. Overall, good visual outcome (20/200 or better) was achieved in 51% of the whole study group, and in 70.6% of eyes with giant tears, 62.1% of eyes with difficult RD, 44.8% of eyes with PVR, 33.3% of eyes with macular holes, and 28.6% of eyes with trauma (p=0.0382). Logistic regression analysis identified initial visual acuity of 20/200 or better as a factor associated with good visual outcome and occurrence of retinal redetachment/hypotony and old age ( > or = 50 years) as factors negatively associated with good visual outcome. CONCLUSIONS: The low redetachment rate might be due to prophylactic 360 degree retinopexy. Giant tears had the best visual outcome. Redetachment/hypotony had a negative impact on achievement of good visual outcome and were associated with PVR and trauma.

Retinal periphlebitis resembling frosted branch angiitis with nonperfused central retinal vein occlusion.

PURPOSE: To report the unusual association between severe retinal periphlebitis resembling frosted branch angiitis and nonperfused central retinal vein occlusion (CRVO). METHODS: Observational case reports. RESULTS: Patient 1 was a 28-year-old man who presented with extensive sheathing involving all retinal veins in one eye followed by nonperfused CRVO. Twenty-seven months after initial presentation, he developed perfused CRVO in the other eye followed by periphlebitis that progressed into nonperfused CRVO. Patient 2 was a 47-year-old man who presented with unilateral severe retinal periphlebitis associated with nonperfused CRVO. Despite systemic administration of corticosteroid therapy, rubeosis iridis developed in both patients and neovascular glaucoma developed in Patient 1 despite full panretinal photocoagulation. Extensive systemic workup and coagulation studies were unremarkable except for the presence of antiphospholipid antibodies in both patients and elevated plasma homocysteine level in Patient 2. CONCLUSIONS: Severe retinal periphlebitis complicated by nonperfused CRVO is associated with poor visual outcome despite appropriate medical and surgical treatment.

Hyperhomocysteinemia and retinal vascular occlusive disease.

PURPOSE: Elevated plasma homocysteine is an independent risk factor for thrombosis and vascular disease. This prospective study compared plasma total homocysteine levels in patients with retinal vascular occlusive disease and in matched healthy controls. METHODS: We measured plasma total homocysteine in 56 consecutive patients with recently diagnosed retinal vascular occlusive disease: 36 had central retinal vein occlusion, 12 branch retinal vein occlusion, and 8 retinal artery occlusion, and compared them with 59 age- and sex-matched healthy controls. Homocysteine levels were determined by high-performance liquid chromatography with electrochemical detection. Hyperhomocysteinemia was defined as a plasma homocysteine level above the 95th percentile in the control group (13.6 micromol/L). RESULTS: Mean plasma total homocysteine levels were significantly higher in patients than controls (16.1 +/- 8.3 vs. 8.96 +/- 5.6 micromol/L p < 0.001). Mean homocysteine levels were significantly higher in the retinal vein occlusion and retinal artery occlusion groups than the control group (15.3 +/- 8.2 and 20.95 +/- 6.9 vs 8.96 +/- 5.6 micromol/L, p < 0.001). Estimates of the relative risk indicated that the risk of hyperhomocysteinemia was significantly higher in patients with retinal vascular occlusive disease than controls. Hyperhomocysteinemia was present in 37 (66.1%) of the 56 patients with retinal vascular occlusive disease but only 2 (3.4%) controls (odds ratio [OR] 47.5, 95% confidence interval [CI] 9.8-149.9). Hyperhomocysteinemia was present in 29 (60.4%) of the patients with retinal vein occlusion (OR 43.5, 95% CI 8.77-141.93) and in 6 (75%) patients with retinal artery occlusion (OR 85.5, 95% CI 7.49-1,173.1). CONCLUSIONS: High plasma homocysteine is a risk factor for retinal vascular occlusive disease so it may be useful to measure homocysteine in the management of these patients. A randomized, controlled trial is required to study the effect of lowering with homocysteine folic acid and other B vitamins on the risk of recurrent vascular occlusion in the same eye or its development in the fellow eye.