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Purpose: To identify systemic factors associated with the development of central serous chorioretinopathy (CSCR)., Design: Retrospective, case-control study., Participants and Controls: 312 cases and 312 controls., Results: By use of a multivariate analysis, the previously described risk factors, systemic steroid use (odds ratio [OR], 37.1; 95% confidence interval [CI], 6.2-221.8), and pregnancy (OR, 7.1; 95% CI, 1.0-50.7), were strongly associated with CSCR. Additional risk factors identified by this study include antibiotic use (OR, 6.2; 95% CI, 1.0-37.9), alcohol use (OR, 4.9; 95% CI, 1.5-16.3), untreated hypertension (OR, 3.3; 95% CI, 1.3-8.5), and allergic respiratory disease (OR, 2.5; 95% CI, 1.2-5.1)., Conclusions: A wide variety of systemic factors are associated with CSCR. Prospective studies are warranted to evaluate the nature and significance of these associations further.

Purpose: To investigate the role of the gap junction protein, connexin-43 (Cx43) in the maintenance of retinal vascular homeostasis in diabetic retinopathy., Methods: In human retinal pericytes (HRPs) and bovine retinal pericytes (BRPs) grown for 7 days in normal (5 mM) or high (30 mM)-glucose medium, the Cx43 protein level was determined by Western blot analysis. Parallel experiments were performed in HRPs to determine the Cx43 mRNA level by RT-PCR, the distribution and localization of Cx43 protein by immunostaining, and gap junction intercellular communication (GJIC) activity by a scrape-loading dye transfer technique. Distribution and localization of Cx43 protein was also determined in pericyte-endothelial cell cocultures., Results: Western blot analysis of the Cx43 protein level in HRPs and BRPs indicated reduced Cx43 expression in the high-glucose condition (69.1% +/- 17% of control, P = 0.004; 62.3% +/- 19% of control, P = 0.001, respectively). The Cx43 mRNA level in HRPs grown in high-glucose medium also showed significant reduction (71.4% +/- 16.8% of control, P = 0.02). The relative number of Cx43 plaques indicative of Cx43 localization at specific sites of contact between adjacent cells showed significant reduction in the high-glucose condition (61% +/- 10% of control, P = 0.002); similarly, a significant reduction in the number of plaques was observed in cocultures grown in high-glucose medium compared with those in normal medium (59.4% +/- 29% of control, P = 0.001). Cells with reduced Cx43 expression showed significantly reduced transfer of lucifer yellow (61% +/- 13% of control, P = 0.001; r = 0.9)., Conclusions: High-glucose-induced downregulation of Cx43 expression and inhibition of GJIC in retinal pericytes may play a role in the disruption of vascular homeostasis in diabetic retinopathy.

Purpose: To investigate and to identify endocrine and metabolic abnormalities in patients with central serous chorioretinopathy (CSCR)., Design: Observational case series., Participants: Twenty-four patients with CSCR., Methods: Serum and urinary catecholamines, glucocorticoids, mineralocorticoids, serum testosterone, and thyroid-stimulating hormone (TSH) function were evaluated prospectively., Results: Fifty percent (12 of 24) of patients with active acute CSCR showed elevated 24-hour urine cortisol or tetrahydroaldosterone levels. Serum aldosterone levels were low in 7 of 24 (29.1%) patients. Single morning plasma catecholamine levels were elevated in 7 of 24 patients, although 24-hour urine metanephrines (catecholamine breakdown products) were normal. Serum testosterone and TSH levels were normal in nearly all (23 of 24) patients., Conclusion: Many patients with acute CSCR have elevated 24-hour urine corticosteroids, which may contribute to the pathogenesis of the disorder. Endogenous mineralocorticoid dysfunction is a newly described feature of CSCR.

Impairment of retinal vascular homeostasis is associated with the development and progression of diabetic retinopathy involving gap junction intercellular communication (GJIC) activity. The principal gap junction protein of intercellular communication, connexin, was investigated to determine the effects of high glucose concentrations on the expression of endothelial-specific connexins (Cx37, Cx40, and Cx43), connexin phosphorylation pattern, and GJIC activity. Rat microvascular endothelial (RME) cells grown in high (30 mmol/l)-glucose medium for 9 days had reduced Cx43 expression: Cx43 mRNA (68 +/- 13% of control; P = 0.019, n = 5) and protein (55.6 +/- 16% of control; P = 0.003, n = 5) levels were reduced; however, Cx37 and Cx40 expression was not affected. Using alkaline phosphatase and Western blot analyses, we identified three forms of Cx43: a nonphosphorylated form (P0) and two phosphorylated forms (P1 and P2). Expression of all three forms was decreased in cells grown in high-glucose medium: PO, 73 +/- 15% of control (P = 0.04); P1, 57 +/- 16% of control (P = 0.01); and P2, 42 +/- 22% of control (P = 0.006). Using immunofluorescence microscopy, we observed Cx43 localization at specific sites of contact (plaques) between adjacent cells. In cells grown in high-glucose medium, we observed reduced plaque counts (63 +/- 6% of control; P = 0.009) and decreased intensity of Cx43 immunofluorescence compared with cells grown in normal medium. Furthermore, using scrape load dye transfer (SLDT) technique, we found that these cells exhibited reduced GJIC activity (60% of control; P = 0.01, n = 5). The reduction in GJIC activity correlated with the decreased Cx43 protein levels (r = 0.9). These results indicate that high glucose concentrations inhibited GJIC activity by reducing Cx43 synthesis in RME cells. Impaired intercellular communication may contribute to breakdown of homeostatic balance in diabetic microangiopathy.

Background: Abnormalities of dark adaptation have been documented in patients with age-related macular degeneration (AMD), but the relationship with the various forms of this disorder has not been studied systematically., Methods: Dark-adapted retinal sensitivities and kinetics of dark adaptation were studied using a Humphrey visual field analyzer adapted for these purposes in patients over 64 years of age. One eye per patient was studied. Study eyes had a normal visual acuity and macular drusen only. The fellow eye was categorized as follows: group I, pigment epithelial detachments and tears of the retinal pigment epithelium (RPE); group II, choroidal neovascularization; and group III, drusen only. The results of psychophysical tests of the study eyes (group I and II and one eye of group III patients) were compared with one another and with older patients without evidence of AMD (group IV)., Results: Retinal sensitivity was found to be most consistently abnormal nearest the fovea. The time course of dark adaptation was prolonged beyond 45 min in 10/11 patients (91%) in group I, 6/10 patients (60%) in group II, and 6/10 (60%) in group III and 1/11 (9%) in group IV., Conclusion: In a high proportion of patients with visual loss from AMD in one eye, the fellow eye shows abnormal dark adaptation. These changes appear to be most pronounced in patients with detachments of the RPE in the fellow eye.

Purpose: The localization and site of action of photosensitizers in the eye may be important for photodynamic therapy for fundus disorders but remain poorly understood for most agents. We investigated the intraocular localization of xanthene, phthalocyanine, and chlorin photosensitizers by using fluorescence microscopy and digital fundus fluorescence angiography., Methods: Rose bengal (40 mg/kg), aluminum phthalocyanine tetrasulfonate (CASPc) (5 mg/kg), or chlorin e6 (2 mg/kg) was intravenously administered to albino rabbits. The eyes were enucleated and examined by means of fluorescence microscopy 5, 20, 60, and 120 minutes and 24 hours after dye injection. In vivo digital fundus fluorescence angiography with use of rose bengal (2-4 mg/kg), CASPc (2 mg/kg), and chlorin e6 (2 mg/kg) was performed., Results: For all agents studied pathologically, there was moderate fluorescence from the choroid and retinal pigment epithelium 5 minutes after dye injection. Mild fluorescence detected from the photoreceptor outer segments at 5 minutes was increased at 20 minutes. Angiographic studies with use of rose bengal, CASPc, and chlorin e6 revealed differences in the pattern and rate of photosensitizer accumulation., Conclusions: Rose bengal, CASPc, and chlorin e6 accumulate rapidly in the choroid and retinal pigment epithelium and less rapidly in the outer retina. Differences in ocular localization of these photosensitizers were demonstrated. The significance of these findings for potential photodynamic therapy with these agents requires further investigation.

Objective: To describe early and unusual features in 16 patients with deferoxamine-induced retinal toxicity and to assess the role of diagnostic tests in the diagnosis and management of patients with the disorder., Design: Retrospective, observational case series., Participants: Sixteen patients with deferoxamine retinopathy identified from members of the Vitreous, Retina, and Macula societies of the United States. INTERVENTION/TESTING: The patients underwent complete ophthalmologic examination. Most patients were also evaluated by fluorescein angiography and electrophysiologic testing. The diagnosis was based on the medical history, systemic and ocular findings, and the results of electrophysiologic tests., Main Outcome Measures: Ocular symptoms, ophthalmoscopic, fluoroangiographic, and electrophysiologic findings., Results: We confirmed previously reported findings in patients with established disease, including macular and/or peripheral pigmentary changes, reduced electroretinographic (ERG) amplitudes, and reduced electrooculographic (EOG) light-peak to dark-trough ratios. Peripapillary, papillomacular, and paramacular patterns of retinal pigment epithelial (RPE) degeneration were each observed in one patient. Diffuse RPE or outer retinal fluorescence by fluorescein angiography was a marker for active retinopathy both at the onset of disease and during recurrence and preceded the development of RPE pigment mottling., Conclusions: Unusual patterns of deferoxamine retinopathy may occur in addition to the foveomacular and/or peripheral patterns previously described. Fluorescein angiography is particularly useful for determining whether there is ongoing retinal/RPE injury. ERG and EOG testing may indicate earlier or more widespread injury than is suggested by fundus examination alone. Patients who do not discontinue deferoxamine after the development of retinopathy risk further retinal/RPE injury and visual deterioration.

Purpose: To detect and identify, in situ, the lipid composition of drusen, diffuse Bruch's membrane deposits, and sclera in aging human eyes using hot-stage polarizing microscopy (HSPM), a method that allows qualitative determination of lipid subtypes within histologic sections based on morphology and melting temperatures of liquid crystals as monitored by birefringence during heating and cooling., Methods: Full-thickness buttons of the central macula and the periphery of human eyes from 17 patients were fixed in 5% calcium-buffered formalin. Frozen sections were stained with oil red O or Sudan black or were analyzed by HSPM., Results: Birefringent anisotropic droplets ("maltese crosses") with melting characteristics of cholesterol esters were identified within diffuse Bruch's membrane deposits, drusen, and sclera. Deposits that melted from crystal to oil without any maltese cross formation when cooled were present in the sclera and are consistent with triglyceride-rich deposits. Deposits with optical properties consistent with phospholipids were identified in a single aged eye. Eyes from young donors did not show these changes., Conclusions: HSPM is a valuable technique for evaluating the nature of lipid deposits in aging eyes. Further studies are warranted to determine whether similar changes are also present in eyes with age-related macular degeneration.

A 35-year-old patient with cytomegalovirus (CMV) retinitis secondary to acquired immunodeficiency syndrome (AIDS) underwent pars plana vitrectomy and fluid-gas-silicone exchange for retinal detachment. Three weeks following surgery and additional laser photocoagulation, extensive retinal surface emulsification was noted. It masked the retinal surface and demonstrated shifting in subsequent examinations. This case stresses the importance of careful and close follow-up after pars plana vitrectomy and silicone oil injection. Silicone oil emulsification may in some cases require removal of the emulsified fluid or silicone oil exchange, but in others such as our case, shifting of the emulsified silicone oil may allow evaluation of the nonobscured retina.

With the rise of popularity of phacoemulsification as the preferred surgical method for cataract extraction, there has been an increased incidence of posterior dislocation of lens fragments. The appropriate management of this complication both during and after cataract extraction is discussed in this review. It is suggested that vigorous attempts by the cataract surgeon to retrieve intravitreal lens fragments should be avoided. Timely referral to a posterior segment surgeon for pars plana vitrectomy and removal of lens fragments can result in good visual outcome. Complications, such as glaucoma and retinal detachment, may develop in some cases. The importance of careful clinical follow-up is emphasized.

Objective: The purpose of the study is to investigate the relationship between inhaled or intranasal adrenergic agonists and corticosteroids and the development of central serous chorioretinopathy (CSC)., Design: The medical records of three patients with CSC who were found to use inhaled adrenergic agents or corticosteroids or both were identified prospectively. A survey of members of the Retina, Macula, and Vitreous societies and the National Registry of Drug-Induced Ocular Side Effects identified three additional cases., Results: Six patients with CSC were found to be chronic users of corticosteroid (four patients) or both beta adrenergic agonist and corticosteroid (two patients) metered dose inhalers or nasal sprays. In three cases, there was a close temporal correlation between the use of a corticosteroid nasal spray and the development of CSC., Conclusions: These findings suggest that, in patients who are susceptible, the periocular or systemic absorption of inhaled corticosteroids may be sufficient to produce CSC in humans, supporting previous hypotheses regarding the pathogenesis of the disorder. Further studies are needed to confirm this association and to determine whether inhaled adrenergic agents also contribute to the development of this disorder. Patients in whom CSC develops while using corticosteroid inhalers or nasal sprays should be alerted to the possible relationship between CSC and these agents.

Background: Choroidal metastases from renal cell carcinoma are uncommon. The authors investigated the clinical characteristics of patients with renal cell carcinoma in whom choroidal metastases developed., Methods: The clinical records of five patients with histopathologically confirmed renal cell carcinoma and choroidal metastases were reviewed retrospectively., Results: In four patients, choroidal metastases were either the sole initial manifestation of disease or were the initial manifestation of metastatic disease. The interval from nephrectomy to the onset of ocular signs ranged from 6 to 18 years. A reddish-orange appearance of the tumor was present in two patients, but no pathognomonic features distinguishing these tumors from other choroidal metastases were identified., Conclusions: Ocular metastases may precede the diagnosis of renal cell carcinoma or may follow it by years or decades. This interval between its ocular and systemic presentation may be so prolonged as to obscure the relation between the choroidal metastases and the primary tumor. In patients with amelanotic or reddish choroidal lesions without known metastatic disease, evaluation of the kidney may be warranted as part of a metastatic workup to exclude metastatic renal cell carcinoma.

Purpose: Photodynamic therapy (PDT) using the photosensitizer Benzoporphyrin derivative monoacid (BPD-MA or verteporfin) is currently under investigation for the treatment of choroidal neovascularization. We investigated the localization of this photosensitizer using fluorescence microscopy and quantified its presence in ocular tissues after porphyrin extraction using fluorescence spectroscopy., Methods: Albino rabbits were administered 2mg/kg BPD-MA pre-complexed with low density lipoprotein (LDL) intravenously, or given no treatment. The eyes were enucleated at intervals between 5 minutes and 24 hours after dye injection and were studied with light and fluorescence microscopy, or dissected for porphyrin extraction., Results: At 5 minutes after dye injection, there was bright fluorescence from the choroid and retinal pigment epithelium (RPE) with trace retinal outer segment fluorescence. After 20 minutes, there was increased photoreceptor outer segment and RPE fluorescence but decreased choroidal fluorescence. By 2 hours no fluorescence remained in either the choroid or the photoreceptors and there was diminished fluorescence of the RPE. Trace RPE fluorescence was still visible at 24 hours. Fluorescence localization of liposomal BPD (2mg/kg) at the earliest (5 minutes) time point was indistinguishable from that of the BPD-LDL complex. Using spectrofluorimetry, the highest BPD-MA levels from the eye were measured in the retina/RPE/uvea complex with lower levels measured from the sclera and other tissues., Conclusions: BPD-MA with LDL rapidly accumulates in the choroid, RPE, and photoreceptors after intravenous injection. Future studies of PDT with BPD-MA for the treatment of fundus disorders may need to address the relationship between dye localization and photodynamically-mediated injury.

Purpose: The authors tested the intravitreal toxicity of four commonly employed dental adhesives to determine their suitability as retinal adhesives., Methods: Two glass ionomers, a polycarboxylate, and a composite resin (Ketac-Bond Radiopaque Poly Maleic Acid [ESPE, Oberbay, Germany], Vitrebond Light Cure Glass Ionomer [3M, St. Paul, MN], Carbchem Zinc Polycarboxylate Cement [PSP Dental Company, Kent, United Kingdom], and Kerr Porcelite Dual Cure [Kerr, Romulus, MI]) were reconstituted according to the manufacturer's recommendations, and 0.1 mliter was injected separately into the vitreous cavity of New Zealand white rabbits. Serial slit-lamp and funduscopic evaluations were performed up to 3 months after injection. Selected eyes were studied angiographically and histopathologically., Results: Intravitreal administration of the glass ionomers Ketac-bond or Vitrebond lead to intense vitritis within the first weeks. Necrotic retinal detachments ultimately developed in these eyes, along with those administered the polycarboxylate cement Carbchem. Eyes injected with the composite resin Porcelite Dual Cure showed no ophthalmoscopic evidence of vitreous or retinal toxicity and no angiographic evidence of vascular toxicity. Histopathology of the eyes with this intravitreal composite resin cement revealed mild disorganization of photoreceptor nuclei and outer segments., Conclusions: Among the agents studied, the dual-cure composite resin cement Porcelite showed the least ocular toxicity. Further studies to evaluate its intraocular toxicity and efficacy as a retinal adhesive are warranted.

Purpose: To describe the clinical features, surgical management, and outcome of patients with uveal melanoma who presented with or later developed a rhegmatogenous retinal detachment., Methods: We retrospectively identified four patients who presented with uveal melanoma and rhegmatogenous retinal detachment simultaneously and six patients in whom a rhegmatogenous retinal detachment developed 11-100 months (mean, 44.8 months) after radiotherapy for a choroidal melanoma., Results: All four patients with simultaneous presentation of uveal melanoma and retinal detachment underwent successful retinal detachment repair (cases 1 and 4, scleral buckle; case 2, pars plana vitrectomy, and case 3, pneumatic retinoplexy). Rhegmatogenous retinal detachment occurring after proton beam or plaque radiotherapy of uveal melanoma was repaired successfully in five of six patients with scleral buckling alone or in combination with pars plana vitrectomy. In the short follow-up period of this study, we did not observe tumor recurrence either before or after retinal detachment repair., Conclusion: Rhegmatogenous retinal detachment associated with uveal melanoma may be treated successfully using conventional retinal surgical techniques. The benefits of retinal detachment repair must be weighed against any theoretical increased risk of extra-scleral extension of the melanoma. Long-term follow-up evaluation will be required to determine the safety of various retinal detachment repair techniques in these eyes.

1. Idiopathic macular hole was once thought to be an untreatable disorder. During the past several years, surgical techniques have evolved that allow for closure of the macular hole, with restoration of vision in many cases. 2. Perfluorocarbon liquids are an important class of compounds that are under investigation for use in vitreoretinal surgery. The use of these compounds facilitates the performance of intraocular surgical maneuvers in certain difficult-to-manage vitreoretinal disorders. These substances have a high specific gravity and are able to displace water within the eye, facilitating reattachment of the retina in certain types of retinal detachments such as those associated with proliferative vitreoretinopathy and giant retinal tears. PFCLs also aid in the removal of intravitreal lens fragments or foreign bodies and in the repositioning or removal of dislocated intraocular lenses. 3. Ophthalmic nurses and technicians can play an important role in initial screening for these patients. Detection of symptoms may lead to early diagnosis of idiopathic macular hole and subsequent treatment. Patient education emphasizing topics such as the importance of strict postoperative face-down head positioning may be critical for successful surgery.

Objective: To investigate photodynamic therapy of experimental choroidal neovascularization using benzoporphyrin derivative monoacid (Verteporfin)., Methods: Photodynamic therapy using benzoporphyrin derivative monoacid was investigated in cynomolgus monkeys. Following intravenous injection of benzoporphyrin derivative monoacid (1 to 2 mg/kg) complexed with low-density lipoprotein, the eyes were irradiated with 692-nm light at a fluence of 50 to 150 J/cm2 and irradiance of 150 to 600 mW/cm2. Choroidal neovascularization was documented before photodynamic therapy and closure was demonstrated by fundus photography, fluorescein angiography, and light and electron microscopic examination., Results: Following photodynamic therapy, vessels within choroidal neovascularization were occluded, and there was damage to the choroidal neovascularization endothelium and the subjacent choriocapillaris. Damage to the retinal pigment epithelium and photoreceptors was also observed., Conclusion: Photodynamic therapy with lipoprotein-delivered benzoporphyrin derivative monoacid was effective in this animal model of choroidal neovascularization and may be a promising, potentially selective, therapy for choroidal neovascularization.

Hutchinson-Tay choroiditis, Holthouse-Batten chorioretinitis, Doyne's honeycomb familial choroiditis and Malattia levantinese are various names which have been used to denote dominantly inherited drusen. Whether these represent one or more than one disorder remains unclear because of the quality of the illustrations and incomplete information in some of the original articles. The early descriptions of these various conditions have been reviewed. Evidence is presented that Doyne's honeycomb familial choroiditis and Malattia levantinese are disorders which can be distinguished from each other by clinical criteria.

Purpose: The purposes of this study are to identify clinical features in eyes with suprachoroidal hemorrhage which portend a poor visual prognosis and to determine visual outcome in these eyes after secondary surgical management of suprachoroidal hemorrhage., Methods: This was a retrospective study of 106 patients with suprachoroidal hemorrhages occurring in association with trauma (35), cataract surgery (30), glaucoma surgery (17), penetrating keratoplasty (6), corneal perforation (5), secondary lens implantation (3), pars plana vitrectomy (3), and other causes (7)., Results: Five (10%) of 49 eyes with a suprachoroidal hemorrhage and an initial retinal detachment had a visual outcome of 20/200 or better compared with 21 (43%) of 49 eyes without a retinal detachment. The presence or absence or a retinal detachment could not be determined in eight patients and all eight of these patients had a poor visual outcome. Sixteen (20%) of 82 eyes with a 360 degrees suprachoroidal hemorrhage had a visual outcome of 20/200 or better compared with 10 (47%) of 21 for those with suprachoroidal hemorrhage limited to one or two quadrants. The extent of the hemorrhage could not be determined in three eyes. Overall, 34% (14/41) of the patients with suprachoroidal hemorrhage who had a secondary surgical procedure achieved a visual outcome of 20/200 or better. Forty-three percent (6/14) who had a suprachoroidal hemorrhage during or after cataract surgery and who were treated with secondary surgical management achieved a visual outcome of 20/200 or greater., Conclusion: Clinical features associated with a poorer visual outcome included initial or indeterminate retinal detachment and 360 degrees suprachoroidal hemorrhage. Limited suprachoroidal hemorrhage without initial retinal detachment usually has a good visual prognosis and does not usually require secondary surgical intervention. However, if the former complication is present, secondary surgical intervention should be considered.

Six patients with rheumatoid arthritis (eight eyes) presented with small paracentral perforating corneal ulcers in otherwise quiet eyes. Initial management in five patients (seven eyes) consisted of systemic immunosuppression and therapeutic tissue adhesive with a bandage contact lens or tectonic keratoplasty. Ulceration recurred in all of these eyes, and recurrent ulcers treated with repeat tectonic keratoplasty or therapeutic tissue adhesive and a bandage contact lens all developed recurrent ulceration. The introduction of topical cyclosporine therapy in five eyes with recurrent corneal ulceration was associated with arrest of keratolysis and rapid re-epithelialization of the ulcer in all cases. One corneal ulcer was successfully treated initially with topical cyclosporine, tissue adhesive, and a bandage contact lens. In patients with rheumatoid arthritis and small paracentral corneal ulcerations or perforations, application of tissue adhesive and a bandage contact lens and introduction of topical cyclosporine may be the preferred initial treatment.

The Barraquer microkeratome may be used to cut donor and host lenticules for lamellar keratoplasty. Eleven eyes of nine patients with visually symptomatic anterior corneal opacification underwent optical lamellar keratoplasty using this technique. In three eyes, this was combined with extracapsular cataract extraction and posterior chamber intraocular lens implantation. Preoperatively, four patients had anterior stromal scars in the visual axis. There were three patients with Reis-Bückler, and two with granular corneal dystrophy. Postoperatively, visual acuity improved in ten eyes and was unchanged in one. We conclude that the Barraquer microkeratome facilitates lamellar keratoplasty and may be successfully combined with extracapsular cataract extraction and posterior chamber intraocular lens implantation. Optical lamellar keratoplasty may be an alternative to penetrating keratoplasty in selected patients with localized anterior corneal opacification.