Combined intravitreal anti-VEGF and verteporfin photodynamic therapy for juxtafoveal and extrafoveal choroidal neovascularization as an alternative to laser photocoagulation.

PURPOSE: To evaluate anti-VEGF and photodynamic therapy (PDT) for juxtafoveal and extrafoveal choroidal neovascularization (CNV) due to age-related macular degeneration (ARMD), ocular histoplasmosis syndrome (OHS), and degenerative myopia. METHODS: A total of 10 eyes with juxtafoveal or extrafoveal choroidal neovascularization underwent intravitreal anti-VEGF therapy combined with verteporfin PDT (689 nm). Most treatments consisted of PDT every 12 weeks and either ranibizumab 0.5 mg every 4 weeks or bevacizumab 1.25 mg every 6 weeks, initiated concurrently. Retreatment criteria were persistent exudative signs on optical coherence tomography or fluorescein angiography. RESULTS: Presenting visual acuity (VA) ranged from 20/20 to 20/60 (mean log MAR+/-SD, 0.338+/-0.16 (20/44 equivalent)). After a mean follow-up of 17.5 months, it ranged from 20/15 to 20/40 (mean log MAR+/-SD, 0.150+/-0.14 (20/28 equivalent); P=0.027, paired t-test). Six eyes improved by > or = 2 lines and four remained within 2 lines of initial VA. Non-ARMD eyes required much fewer treatments than ARMD eyes. All five non-ARMD eyes and three of five ARMD eyes showed no CNV activity at least 5 months after last treatment. CONCLUSIONS: Anti-VEGF therapy and PDT can preserve good visual function and may be suited to some cases of nonfoveal CNV. ARMD eyes require longer courses of treatment than non-ARMD eyes.

Longitudinal observations on mutations conferring ganciclovir resistance in patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis: The Cytomegalovirus and Viral Resistance Study Group Report Number 8.

PURPOSE: Cytomegalovirus retinitis is the most common intraocular infection in patients with acquired immunodeficiency syndrome (AIDS). With prolonged suppressive anticytomegalovirus maintenance therapy, resistance occurs in over 25% of patients. We evaluated longitudinal changes in the cytomegalovirus genotype in patients with cytomegalovirus retinitis who developed ganciclovir resistance that was demonstrated in either the blood or urine. METHODS: Patients with AIDS and previously untreated cytomegalovirus retinitis were followed prospectively for the occurrence of resistance while on treatment. Blood and urine specimens were obtained periodically for cytomegalovirus culture according to a predetermined schedule. Positive isolates were tested for phenotypic susceptibility and for mutations in the UL97 and UL54 genes. RESULTS: A mutation conferring resistance to ganciclovir in either the UL97 or UL54 gene was detected in 18 patients. In general, patients with a genotypically resistant virus developed increasing phenotypic resistance over time. There was a suggestion that unless therapy was changed, UL97 mutations tended to persist. In seven of eight patients, the mutations identified in isolates from the blood and urine were identical. In selected patients, there was a suggestion that a mixed population of cytomegalovirus might be present. Progression of the retinitis in an involved eye (15 of 18), contralateral eye retinitis (10 of 11), and extraocular cytomegalovirus disease (5 of 18) occurred commonly among patients with resistant virus. CONCLUSION: Resistance-conferring mutations in the cytomegalovirus genome emerge and may persist when the selective pressure for resistance is maintained. Some patients appear to harbor complex subpopulations of virus with different mutations and different levels of phenotypic resistance. Changes in therapy may result in a shift in virus population and changes in the cytomegalovirus genotype identified.

Laser photocoagulation for choroidal neovascularization associated with sympathetic ophthalmia.

PURPOSE: To present a case of choroidal neovascularization associated with sympathetic ophthalmia successfully treated with photocoagulation. DESIGN: Interventional case report. METHODS: A 41-year-old man with a history of penetrating injury right eye, as well as sympathetic ophthalmia left eye, developed a classic choroidal neovascular membrane that threatened the center of the fovea. RESULTS: The patient was treated with argon laser photocoagulation. He has maintained stable visual acuity without evidence of recurrence of the membrane with 4 years' follow-up. CONCLUSION: Thermal laser should be considered as a treatment option in cases of choroidal neovascularization associated with sympathetic ophthalmia.

Sympathetic ophthalmia associated with pars plana vitrectomy without antecedent penetrating trauma.

PURPOSE: To evaluate, describe, and categorize the clinical presentation, clinical course, histopathology, and response to therapy in patients without a history of penetrating ocular trauma who developed sympathetic ophthalmia following pars plana vitrectomy. METHODS: The records of patients without a history of trauma who underwent pars plana vitrectomy and developed sympathetic ophthalmia were retrospectively reviewed. Cases were analyzed with respect to clinical presentation, fluorescein angiographic findings, anatomic and visual outcomes, histopathology, and response to therapy. RESULTS: Eight eyes were identified. The median age at presentation was 55 years, with a range of 14 to 62 years. The time from vitrectomy to diagnosis of sympathetic ophthalmia ranged from 2 months to greater than 2 years, with a median of 7 months. Six of eight patients (75%) presented with anterior chamber reaction. All eight patients presented with a vitreous inflammatory response. The optic nerve was inflamed clinically or angiographically in four of eight cases (50%). Small yellow-white sub-retinal pigment epithelial deposits were present in four of eight cases (50%). Two eyes had lesions characterized as multifocal choroiditis. One eye had larger yellow placoid-like lesions. One eye presented with vitritis but no retinal lesions. Subretinal choroidal neovascularization was noted in the inciting eye of one patient. Vision improved in the sympathizing eye with immunosuppressive therapy in five of eight cases (62.5%). CONCLUSIONS: Sympathetic ophthalmia can be seen following pars plana vitrectomy in patients without penetrating injuries or a history of trauma. Indeed, it may be seen after successful vitrectomy for retinal detachment. Diverse clinical presentations are possible, and persistent or atypical uveitis following vitrectomy should alert the surgeon to the development of sympathetic ophthalmia.

Mutations conferring ganciclovir resistance in a cohort of patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis.

Cytomegalovirus (CMV) retinitis is among the most common opportunistic infections in patients with acquired immunodeficiency syndrome. In a prospective study of 210 patients with CMV retinitis, 26 were identified as having either a phenotypic or a genotypic ganciclovir-resistant isolate from either blood or urine cultures. For blood culture isolates with an IC(50) >6.0 microm for ganciclovir, the sensitivity and specificity for detecting a UL97 mutation were 95% and 98%, respectively, whereas for an IC(50) >8.0 microM they were 79% and 99%, respectively. Although there were trade-offs between the 2 thresholds for blood culture isolates, for urine culture isolates an IC(50) >8.0 microM appeared to be better at identifying genotypic resistance. UL97 mutations identified in both the blood and urine cultures of individual patients were identical in 87.5% of cases. High-level ganciclovir resistance (IC(50), >30 microM) typically, but not invariably, was associated with a mutation in both the UL97 and UL54 genes.

A single-suture technique for placement of the ganciclovir implant.

The ganciclovir implant is a surgically implanted sustained-release drug delivery system used for the treatment of cytomegalovirus retinitis. The device is suspended in the vitreous cavity through a pars plana incision. Previous reports of the surgical procedure have described securing the implant on 1 suture, tied with an external knot. The ends of this suture were left long to avoid sharp ends eroding through the conjunctiva. The wound was then closed with 1 or more additional sutures, with the ends tied and cut short. We describe a technique whereby the wound is closed and the implant secured with a single running suture. The advantages of this technique include efficiency and elimination of exposed knots. We have observed no complications attributable to this technique.

Novel mutations in XLRS1 causing retinoschisis, including first evidence of putative leader sequence change.

Juvenile retinoschisis is an X-linked recessive disease caused by mutations in the XLRS1 gene. We screened 31 new unrelated patients and families for XLRS1 mutations in addition to previously reported mutations for 60 of our families (Retinoschisis Consortium, Hum Mol Genet 1998;7:1185-1192). Twenty-three different mutations including 12 novel ones were identified in 28 patients. Mutations identified in this study include 19 missense mutations, two nonsense mutations, one intragenic deletion, four microdeletions, one insertion, and one intronic sequence substitution that is likely to result in a splice site defect. Two novel mutations, c.38T-->C (L13P) and c.667T-->C (C223R), respectively, present the first genetic evidence for the functional significance of the putative leader peptide sequence and for the functional significance at the carboxyl terminal of the XLRS1 protein beyond the discoidin domain. Mutations in 25 of the families were localized to exons 4-6, emphasizing the critical functional significance of the discoidin domain of the XLRS1 protein.

Randomized, controlled study of the safety and efficacy of intravenous cidofovir for the treatment of relapsing cytomegalovirus retinitis in patients with AIDS.

To assess the effect of intravenous cidofovir on delaying progression of previously treated, relapsing cytomegalovirus (CMV) retinitis, we conducted a randomized, controlled comparison of two maintenance dose levels of cidofovir. One hundred and fifty patients with AIDS and CMV retinitis that had progressed or was persistently active despite treatment with ganciclovir, foscarnet, or both were randomized to receive induction cidofovir, 5 mg/kg once weekly for 2 weeks, then maintenance therapy with either 5 mg/kg or 3 mg/kg once every other week. Concomitant probenecid and intravenous hydration were administered with each cidofovir dose. Retinitis progression was assessed in the first 100 patients by bilateral, full-field retinal photographs read at a central reading center by an ophthalmologist masked to treatment assignment. Incidence of side effects, changes in visual acuity, and mortality were also assessed. Median time to retinitis progression as assessed by retinal photography was not reached (95% confidence interval [CI], 115 days-upper limit not reached) in the 5-mg/kg group, and was 49 days (95% CI, 35-52 days) in the 3-mg/kg group (p = .0006). Dose-dependent asymptomatic proteinuria (39%) and serum creatinine elevation (24%) were the most common adverse events thought to be related to cidofovir. Reversible probenecid reactions including constitutional symptoms and nausea occurred in 65 of 150 (43%) patients. Cidofovir therapy is effective in delaying progression of CMV retinitis that had previously progressed using other anti-CMV therapies.

Results of peripheral laser photocoagulation in pars planitis.

PURPOSE: To determine the effect of peripheral retinal laser photocoagulation (PLP) on visual acuity, intraocular inflammation, and other ocular findings, including retinal neovascularization in eyes with pars planitis. METHODS: A retrospective chart review of eyes with pars planitis that had undergone PLP. RESULTS: Twenty-two eyes in 17 patients with pars planitis had undergone treatment with PLP at 2 centers. The mean age at the time of treatment was 19.3 years. Following treatment, mean follow-up was 16.3 months (range, 6 to 37 months). Mean visual acuity was 20/60 preoperatively and 20/50 postoperatively. This level of improvement was not statistically significant (P > .10), but there was a statistically significant decrease in the use of corticosteroids between the preoperative examination and the last postoperative examination (86% versus 27%, P < .05). There was also a statistically significant decrease in vitritis at the last follow-up (P = .0008) and a decrease in neovascularization of the vitreous base (P = .03) and in clinically apparent cystoid macular edema (P = .02). Epiretinal membranes were noted in 23% of eyes preoperatively and in 45% of eyes postoperatively. Only one of these epiretinal membranes was considered to be visually significant. One eye developed a tonic dilated pupil, which slowly improved. CONCLUSIONS: Although the long-term natural history of clinical findings in pars planitis is not well documented, PLP appears to decrease the need for corticosteroids while stabilizing visual acuity. It also appears to decrease vitreous inflammation. PLP has few complications and should be considered in patients with pars planitis who are unresponsive or have adverse reactions to corticosteroids.

Iritis and hypotony after treatment with intravenous cidofovir for cytomegalovirus retinitis.

OBJECTIVE: To describe intraocular inflammation due to treatment with intravenous cidofovir dihydrate for cytomegalovirus retinitis. DESIGN: Retrospective cohort. SETTING: Three university outpatient ophthalmology clinics. PATIENTS: All patients treated with intravenous cidofovir therapy before October 31, 1996. INTERVENTION: Treatment with intravenous cidofovir was given according to standardized protocols. Intraocular inflammation was treated according to the best medical judgment. MAIN OUTCOME MEASURES: The presence of new intraocular inflammation, the severity of inflammation, visual acuity, and intraocular pressure. RESULTS: Eleven cases of iritis (26%) occurred among 43 patients. In 6 cases, the iritis was bilateral. Patients who experienced iritis were more likely to have been previously treated for cytomegalovirus retinitis (P = .03), to be diabetic (P = .05), or to be receiving protease inhibitors (P < .001). Four patients and 15 control subjects had also taken rifabutin (P = .70). The onset of iritis occurred at a mean (+/-SD) of 4.9 +/- 1.8 days after a cidofovir dose and after a mean (+/-SD) of 4.2 +/- 1.6 doses of cidofovir. Six eyes of 4 patients had hypotony. Five eyes of 5 patients had a persistent decrease in visual acuity of at least 2 Snellen lines. CONCLUSIONS: Acute intraocular inflammation may occur with or without hypotony after intravenous cidofovir therapy, similar to the reactions seen after intravitreous administration. Although the manifestations may be severe, they are manageable with topical corticosteroid therapy in most cases. Cidofovir therapy can be continued in some patients if medical necessity warrants, but recurrent inflammation or permanent hypotony may occur.

Management of varicella zoster virus retinitis in AIDS.

AIMS/BACKGROUND: Varicella zoster virus retinitis (VZVR) in patients with AIDS, also called progressive outer retinal necrosis (PORN), is a necrotising viral retinitis which has resulted in blindness in most patients. The purposes of this study were to investigate the clinical course and visual outcome, and to determine if the choice of a systemic antiviral therapy affected the final visual outcome in patients with VZVR and AIDS. METHODS: A review of the clinical records of 20 patients with VZVR from six centres was performed. Analysis of the clinical characteristics at presentation was performed. Kruskall-Wallis non-parametric one way analysis of variance (KWAOV) of the final visual acuities of patients treated with acyclovir, ganciclovir, foscarnet, or a combination of foscarnet and ganciclovir was carried out. RESULTS: Median follow up was 6 months (range 1.3-26 months). On presentation, 14 of 20 patients (70%) had bilateral disease, and 75% (15 of 20 patients) had previous or concurrent extraocular manifestations of VZV infection. Median initial and final visual acuities were 20/40 and hand movements, respectively. Of 39 eyes involved, 19 eyes (49%) were no light perception at last follow up; 27 eyes (69%) developed rhegmatogenous retinal detachments. Patients treated with combination ganciclovir and foscarnet therapy or ganciclovir alone had significantly better final visual acuity than those treated with either acyclovir or foscarnet (KWAOV: p = 0.0051). CONCLUSIONS: This study represents the second largest series, the longest follow up, and the first analysis of visual outcomes based on medical therapy for AIDS patients with VZVR. Aggressive medical treatment with appropriate systemic antivirals may improve long term visual outcome in patients with VZVR. Acyclovir appears to be relatively ineffective in treating this disease.

Repair of retinal detachments due to herpes varicella-zoster virus retinitis in patients with acquired immune deficiency syndrome.

PURPOSE: The authors characterize surgical techniques and report results for repair of retinal detachments due to varicella-zoster retinitis in patients with acquired immune deficiency syndrome (AIDS). BACKGROUND: Varicella-zoster virus (VZV) retinitis is a distinctly aggressive infection in patients with AIDS. Retinal detachments occur in the majority of such patients, and contribute to their poor visual prognosis. METHODS: A case series of five eyes in four patients with AIDS and retinal detachments due to VZV retinitis is presented, highlighting surgical technique and results. Pars plana vitrectomy, silicone oil tamponade, and endolaser photocoagulation were used in all cases. RESULTS: Apparent contraction of the necrotic retina was observed, requiring large relaxing retinectomies to achieve retinal attachment in three of the five eyes. Follow up after surgery was 4, 6, 15, 29, and 30 months. Four eyes maintained ambulatory vision and the retinas remained attached. CONCLUSION: Vitrectomy with silicone oil tamponade may be used to preserve ambulatory vision in carefully selected patients with AIDS and retinal detachments due to VZV retinitis. Relaxing retinectomy is a useful technique to achieve and maintain retinal attachment.

Cytomegalovirus retinitis.

Cytomegalovirus retinitis is the most common ocular opportunistic infection in patients infected with human immunodeficiency virus and remains a significant cause of visual loss in patients with the acquired immunodeficiency syndrome. Drugs are now available to treat this condition and recent advances in delivery techniques offer promising alternatives to traditional methods.

Combined daily therapy with intravenous ganciclovir and foscarnet for patients with recurrent cytomegalovirus retinitis.

We treated seven patients (nine eyes) who had cytomegalovirus retinitis with daily intravenous ganciclovir plus foscarnet. All patients had demonstrated multiple progressions of retinitis on single-drug therapy, and some were intolerant to induction doses of one or both medications. Before combination therapy, the median number of progressions was five per patient. The mean interval between progressions was 11 weeks, and the mean interval before the final progression was four weeks. While taking combination therapy, two patients showed progression after 14 and 34 weeks. Two patients showed no progression after 17 and 36 weeks of follow-up. Three patients died after five, 14, and 23 weeks, respectively, without progression of retinitis. In every patient, the progression-free interval was longer during combination therapy than the previous progression-free interval during single-drug therapy. In no case was combination therapy stopped because of toxicity. Combination therapy was fairly well tolerated and appeared to prolong the interval to progression and to preserve vision in our patients.

Asymmetric distribution of arteriovenous crossings in the normal retina.

BACKGROUND: Recently, there has been renewed interest in the orientation of the crossing retinal vessels at arteriovenous intersections, particularly as it relates to the risk of branch vein occlusion. Little is known about the distribution of the two types of crossings in the normal retina. METHODS: The authors studied standard fundus photographs of 51 subjects without retinal disease. Arteriovenous crossings were analyzed for fundus location and relative orientation of the crossing vessels (vein-posterior or vein-anterior). FINDINGS: In the superotemporal quadrant, crossings were distributed closer to the optic disc (P < 0.001), and a greater proportion of crossings were vein-posterior (P = 0.01) than in the inferotemporal quadrant. As a result, within a 3-disc diameter (DD) radius of the optic disc, there were significantly more vein-posterior crossings in the superotemporal than in the inferotemporal quadrant (P < 0.001). CONCLUSION: These findings further define normal retinal vascular anatomy and may explain the predilection for branch retinal vein occlusions to occur in the superotemporal quadrant.

Dynamic sodium chemical shift imaging for the study of aqueous humor flow.

Ocular images were obtained using sodium chemical shift imaging (CSI) and 1,4,7,10-tetraazacyclododecane-N,N'N",N"'-tetramethylenephospho nate thulium (III) [Tm(DOTP)5-], a paramagnetic chemical shift reagent. After injecting the shift reagent into the anterior chamber of rabbits, serial imaging was done, monitoring the change in chemical shift with time. Sodium CSI produced images of the eye in three dimensions, quantitatively depicting the spatial and temporal changes in the concentration of a paramagnetic tracer substance. The Tm(DOTP)5- is eliminated from the anterior chamber by first-order kinetics with a half-life of 49 min. These data suggest that this substance is eliminated from the anterior chamber at the same rate as aqueous humor is replaced. Sodium CSI shows promise as a valuable technique for monitoring fluid dynamics in the living eye.