Posterior vitreous detachment with microplasmin alters the retinal penetration of intravitreal bevacizumab (Avastin) in rabbit eyes.

PURPOSE: Intravitreal bevacizumab (BV) (Avastin, Genentech Inc., South San Francisco, CA) is frequently used for the treatment of age-related macular degeneration. Previous studies have demonstrated full-thickness retinal penetration. Intravitreal recombinant microplasmin (MP) has been shown to successfully induce a posterior vitreous detachment (PVD) and vitreous liquefaction in animals. It has been suggested that a PVD may alter the retinal penetration of molecules in the vitreous cavity. The aim of this study was to compare BV retinal penetration in rabbit eyes with and without an MP-induced PVD. METHODS: Twelve adult rabbits were injected with 0.1 mL (0.4 mg) of MP into the vitreous cavity of 1 eye. One week later, the rabbits were injected with 0.05 mL (1.25 mg) of BV into both eyes. Both eyes of 3 rabbits were harvested at 6 hours, 12 hours, 24 hours, and 72 hours after the BV injection. Frozen retinal cross sections were prepared, and BV retinal penetration was evaluated with immunohistochemistry using a fluorescence-labeled antibody against BV. Two eyes from one rabbit were not injected with either agent and used as controls to compare the background autofluorescence. Peripapillary retinal sections were recorded with a digital camera, and intraretinal BV fluorescence-labeled antibody was measured by qualitative photographic interpretation. Two additional rabbits received an intravitreal injection of 0.1 mL of MP in 1 eye. One week later, both eyes from each rabbit were enucleated, and frozen retinal sections were prepared and analyzed with light microscopy to evaluate histologic damage. RESULTS: Full-thickness BV retinal penetration was observed throughout the retina in both eyes of each rabbit. All the MP-injected eyes exhibited increased antibody labeling in retinas evaluated at 6 hours, 12 hours, and 24 hours after BV injection when compared with the contralateral non-MP-injected eyes. By 3 days after BV injection, all eyes demonstrated decreased antibody labeling compared with earlier periods. At 3 days, 1 rabbit showed increased antibody labeling in the retina of the non-MP-injected eye compared with the contralateral MP-injected eye, and 2 rabbits exhibited similar antibody labeling in both eyes. When compared with control eyes, light microscopy demonstrated normal retinal histologic findings in eyes injected only with MP. CONCLUSION: Increased BV retinal penetration is observed initially in eyes with an MP-induced PVD, and the mechanism is likely multifactorial. By 3 days, retinal penetration is similar in eyes with and without a PVD. Although it is difficult to directly extrapolate to humans, our study suggests that a PVD may alter the retinal penetration of BV.

Nonaccidental trauma and peripheral retinal nonperfusion.

PURPOSE: To present fluorescein angiographic findings demonstrating retinal vascular alterations in children subjected to nonaccidental trauma (NAT). DESIGN: Retrospective non-comparative consecutive case series. PARTICIPANTS: Ten eyes of 5 children with the diagnosis of NAT seen at William Beaumont Hospital between August 2007 and December 2008. METHODS: We retrospectively reviewed the charts of 5 consecutive patients with NAT. All patients underwent detailed ophthalmic evaluation under anesthesia, fundus photography, and fluorescein angiography (FA). MAIN OUTCOME MEASURES: The primary outcome was FA findings demonstrating alterations in retinal vascular perfusion, retinal neovascularization, and traction retinal detachment. RESULTS: Seven of 10 eyes demonstrated peripheral retinal nonperfusion by FA, with interruption of both the arterial- and venous-side of the retinal vascular tree. All of the eyes with retinal nonperfusion also presented with preretinal and/or vitreous hemorrhage; none of the eyes without ischemia demonstrated preretinal or vitreous blood. None of the children were born prematurely or had a medical or family history that could otherwise explain their findings. None of the eyes exhibited neovascularization or retinal detachment. Two eyes were treated with laser photocoagulation alone; 2 eyes were treated with vitrectomy alone owing to a nonclearing premacular hemorrhage; 2 eyes were treated with vitrectomy and laser photocoagulation; and 1 eye was observed without treatment. CONCLUSIONS: Peripheral retinal nonperfusion was noted by FA in 7 eyes of infants who were victims of nonaccidental head trauma. Preretinal and/or vitreous hemorrhage may be associated with the development of retinal nonperfusion. Physicians may consider FA in children with known or suspected NAT. The role of prophylactic laser treatment is unclear, and close observation for the development of neovascularization is warranted.

Pharmacologic vitreodynamics and molecular flux.

Several enzymatic agents, such as autologous plasmin enzyme and recombinant microplasmin, are able to cause vitreous liquefaction and a complete posterior vitreous detachment (PVD). Advancements in research have helped to explain the complex interactions that occur in the vitreous cavity after a PVD is created. The development of a PVD is a dynamic process that is thought to have a larger impact on the vitreous cavity milieu than just a separation of the posterior cortical vitreous from the retina. Pharmacologic vitreodynamics attempts to explain the mechanical and biochemical changes that occur at the vitreoretinal junction after a PVD is formed. The flow of molecules into and out of the vitreous cavity and across the vitreoretinal junction is thought to be influenced by the presence or absence of a PVD. A microplasmin-induced PVD has been shown to alter the vitreous levels of several molecules, and a PVD may have a protective role in multiple diseases. Significant progress has been made in the field of pharmacologic vitreodynamics. As we improve our understanding of the molecular flux in the vitreous cavity, pharmacologic vitreodynamics will likely become more important as it may allow for improved manipulation of intravitreal molecules.

Relationship Between Opacity of Cytomegalovirus Retinitis Lesion Borders and Severity of Immunodeficiency Among People With AIDS.

Purpose: To evaluate risk factors for severity of cytomegalovirus (CMV) retinitis lesion whitening (opacity), using a standardized scoring system. Methods: We performed a cross-sectional, observational investigation of all individuals with newly diagnosed AIDS-related CMV retinitis in three randomized clinical trials and one prospective observational study. Opacity was scored by masked readers, using a prospectively defined ordinal 6-point scale. Demographic factors, laboratory data (CD4+, CD8+ T-lymphocyte counts, human immunodeficiency virus [HIV] blood levels), and lesion characteristics (location, size) were compared to the highest opacity score assigned to either eye. Among eyes with active lesions (scores ≥3), factors associated with severe opacity (scores 5, 6) were identified. Results: There were 299 participants (401 eyes with CMV retinitis). In one or more comparisons, increased opacity was associated with lower CD4+ and lower CD8+ T-lymphocyte counts, higher HIV blood level, lack of antiretroviral therapy, male sex, race/ethnicity, and bilateral disease. In eyes with active disease, severe opacity was associated with lower CD4+ T-lymphocyte count, higher HIV blood level, older age, Karnofsky score, lesion size, and bilateral disease. No relationship was identified between opacity and lesion location. Conclusions: Lesion border opacity (resulting from CMV activity) reflects level of immune function; as immunodeficiency becomes worse, CMV activity (and opacity) increases. The positive relationship between opacity and HIV blood level may reflect both immunodeficiency and increased CMV activity caused by transactivation of CMV by HIV. Scoring of opacity may be a useful, standard measure for continued study of CMV retinitis across different settings and populations. (Clinicaltrials.gov number for the HPMPC CMV Retinitis Trial: NCT00000142; Clinicaltrials.gov number for the Monoclonal Antibody CMV Retinitis Trial: NCT00000135; Clinicaltrials.gov number for the Ganciclovir-Cidofovir CMV Retinitis Trial: NCT0000014; Clinicaltrials.gov number for the Longitudinal Study of the Ocular Complications of AIDS: NCT00000168.).

Characteristics of untreated AIDS-related cytomegalovirus retinitis. I. Findings before the era of highly active antiretroviral therapy (1988 to 1994).

PURPOSE: To identify factors related to variations in the appearance of untreated AIDS-related cytomegalovirus (CMV) retinitis in severely immunodeficient individuals before the availability of highly active antiretroviral therapy (HAART) and to draw inferences regarding early events in the natural history of CMV retinitis based on clinical findings. DESIGN: Retrospective, observational case series. METHODS: We evaluated a series of 100 adult patients with AIDS and newly diagnosed CMV retinitis before the HAART era who were not being treated with specific anti-CMV therapy. Demographic factors, ophthalmic findings, and the influence of drug therapy (zidovudine, acyclovir) on lesion characteristics were evaluated. Lesion border opacity was scored using a four-point scale of severity. RESULTS: Lesions could be categorized by type (fulminant/edematous or indolent/granular) in only 66% of eyes. Severe lesion border opacity (4+) was related to presence of zone 1 lesions (P = .032) and greater extent of disease (P = .004). Acyclovir use was associated with less severe opacity (P = .029) and less zone 1 involvement (P = .016). Early lesions were adjacent to vessels in 73% of eyes; the fovea was involved in 13% of eyes. CONCLUSIONS: Lesion location and drug use that affects virus activity may influence the severity of lesion border opacity, a measure that may be more useful than lesion type in future clinical studies of CMV retinitis. In contrast to earlier concepts, CMV retinitis does not seem to be a fovea-sparing disease. Findings in this study can serve as a reference for investigations into possible changes in CMV retinitis since the introduction of HAART.

Characteristics of untreated AIDS-related cytomegalovirus retinitis. II. Findings in the era of highly active antiretroviral therapy (1997 to 2000).

PURPOSE: To describe host characteristics (use of highly active antiretroviral therapy [HAART]; CD4+ T-lymphocyte count; HIV ribonucleic acid [RNA] blood level) of people who were diagnosed with AIDS-related cytomegalovirus (CMV) retinitis after HAART became available and to investigate effects of HAART on ophthalmic findings. DESIGN: Retrospective, observational case series. METHODS: We collected demographic, medical, laboratory, and ophthalmic data for all patients with AIDS and newly diagnosed, untreated CMV retinitis from January 1997 through December 2000 at 10 sites in Los Angeles and Orange Counties, California. RESULTS: The proportions of Hispanic and African-American patients were equivalent to or greater than their prevalences in the AIDS and general populations of Los Angeles County. Most patients (n = 80; 63.5%) were known to be receiving HAART at the time of CMV retinitis diagnosis; only 22 patients (17.5%) were HAART-naïve. Median CD4+ T-lymphocyte count was 15 cells/microl and median HIV RNA blood level was 103,000 copies/ml for all patients, but in 10 patients, CMV retinitis developed despite good immunologic and virologic responses to HAART. When compared with HAART-naïve patients, HAART-failure patients with CMV retinitis had more asymptomatic disease (P = .073), better visual acuity in the better eye (P = .003), more bilateral disease (P = .007), less zone 1 involvement (P = .042), and lower lesion border opacity scores (P = .054). CONCLUSIONS: Most patients with AIDS and newly diagnosed CMV retinitis in an urban setting are HAART-experienced. HAART may influence characteristics of new CMV retinitis lesions at presentation, despite laboratory evidence of treatment failure, possibly because of residual CMV-specific immunity.

An assessment of polymorphonuclear leukocyte rigidity in HIV-infected individuals after immune recovery.

PURPOSE: To determine whether polymorphonuclear leukocytes (PMNs) remain rigid after immune reconstitution in human immunodeficiency virus (HIV)-infected individuals with a history of severe immunosuppression. METHODS: PMN rigidity was measured in vitro in three groups: (1) HIV-infected individuals with a history of CD4+ T-lymphocyte counts of less than 50/microL, but with current counts of more than 200/microL attributable to potent antiretroviral therapy (group 1); (2) HIV-infected individuals whose CD4+ T-lymphocyte counts had always been more than 200/microL (group 2); and (3) HIV-negative control subjects. Rigidity was determined with a cell transit analyzer (containing a micropore filter with 30 identical, 8-microm diameter pores), representing a simple in vitro model of a capillary bed. A longer PMN pore transit time reflects increased PMN rigidity. RESULTS: PMN transit time (median) in group 1 (n = 11) was 3.34 ms, in group 2 (n = 9) was 3.19 ms, and in control subjects (n = 15) was 2.66 ms. PMN rigidity was significantly greater in groups 1 (P = 0.014) and 2 (P = 0.046) than in control subjects (Wilcoxon rank-sum test). A significant difference was not identified between groups 1 and 2 (P = 0.518). CONCLUSIONS: The increased PMN rigidity known to occur in severely immunosuppressed HIV-infected individuals persists after immune reconstitution. Furthermore, PMN rigidity is increased in those HIV-infected individuals who do not have a history of severe immunosuppression. Because PMN rigidity can alter microvascular blood flow, HIV-infected individuals may remain at risk for retinal vascular damage in the era of potent antiretroviral therapy.

Retinal detachments involving the posterior pole in hallermann-streiff syndrome.

PURPOSE: To report a case of Hallermann-Streiff syndrome and bilateral retinal detachments involving the posterior pole. METHODS: Retrospective case report and literature review. RESULTS: A 2-year-old girl with Hallermann-Streiff syndrome was evaluated. Fundus examination showed bilateral exudative retinal detachments involving a significant portion of the posterior pole. The left eye showed several large, cyst-like areas of retinal detachment. The child was observed without treatment, and the subretinal fluid remained stable during the follow-up of 10 months. CONCLUSION: Bilateral retinal detachments can be seen in patients with Hallermann-Streiff syndrome. The etiology is likely to be multifactorial, and uveal effusion may contribute to the exudative fluid. Further evaluation is necessary to determine the visual prognosis and optimal management of patients with exudative retinal detachments associated with Hallermann-Streiff syndrome.

Subretinal abscess after strabismus surgery: case report and literature review.

PURPOSE: The purpose of this study is to describe the first reported case of a subretinal abscess after strabismus surgery and the successful treatment with vitrectomy, intravitreal antibiotics, and cryotherapy. METHODS: This is a retrospective case report and literature review. RESULTS: A 4-year-old boy underwent uncomplicated bilateral medial rectus muscle recession. Within 9 days after surgery, he developed unilateral endophthalmitis with a subretinal abscess at the approximate location of the medial rectus muscle insertion. The rectus muscle-scleral suture was removed, and transscleral cryotherapy was applied to the abscess site. Vitrectomy with injection of intravitreal antibiotics was performed. A bacterial culture of the removed suture was positive for Staphylococcus aureus and sensitive to his antibiotics. By 1 month, the abscess and vitritis had resolved completely. CONCLUSION: This is the first reported case of endophthalmitis with a subretinal abscess occurring after strabismus surgery. In general, endophthalmitis after strabismus surgery has a poor visual prognosis. Early diagnosis and intervention with intravitreal antibiotics and possible vitrectomy may be advantageous for patients with a subretinal abscess.

Serratia marcescens endophthalmitis after 20-gauge pars plana vitrectomy.

PURPOSE: To describe the first reported case of endophthalmitis after 20-gauge vitrectomy caused by Serratia marcescens. METHODS: Retrospective case report. RESULTS: An 86-year-old woman underwent a standard 20-gauge vitrectomy for repair of a chronic rhegmatogenous retinal detachment. All sclerotomies were sutured at the completion of the case. Within 2 days after surgery, she developed severe endophthalmitis. A bacterial culture of her aqueous sample was positive for S. marcescens. Despite the culture-demonstrated sensitivity of this organism to the antibiotics given intravitreally, systemically, and topically to treat this infection, her condition deteriorated, and she developed panophthalmitis, orbital cellulitis, a corneal ulcer, and eventual no light perception vision. CONCLUSIONS: This is the first reported case of S. marcescens endophthalmitis after vitrectomy surgery. Endophthalmitis caused by S. marcescens has a poor visual prognosis and may show an in vivo clinical resistance to antibiotic therapy regardless of in vitro culture sensitivities.

Clear lens extraction with intraocular lens implantation during retinal detachment repair in patients with Acquired Immune Deficiency Syndrome (AIDS) [correction of autoimmune deficiency syndrome] and cytomegalovirus retinitis.

OBJECTIVE: To assess the outcomes of clear lens extraction with intraocular lens (IOL) implantation during repair of retinal detachment by vitrectomy with silicone oil tamponade in patients with acquired immunodeficiency syndrome (AIDS) and cytomegalovirus (CMV) retinitis. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Twelve eyes of 10 patients with AIDS, CMV retinitis, and retinal detachment. INTERVENTION: All patients underwent phacoemulsification with posterior chamber IOL placement at the time of vitrectomy with silicone oil tamponade for repair of retinal detachment. A targeted postoperative refractive error of -5.00 diopters (D) to -3.00 D was chosen in an attempt to counteract the hyperopic effect of silicone oil. MAIN OUTCOME MEASURES: The following factors were evaluated: postoperative visual acuity, refractive error, and intraoperative and postoperative complications. RESULTS: Median follow-up was 7 months (range, 1-46 months). For patients without macular necrosis, median best-corrected preoperative visual acuity was 20/75 (range, 20/20-20/800), and median best postoperative visual acuity was 20/50 (range, 20/20-20/400). Median final visual acuity was 20/140 (range, 20/25 to count fingers at 1 foot). The median postoperative refractive error (spherical equivalent) was -1.00 D (range, -4.00 D to +7.88 D). Reoperation was required in 3 of 12 eyes for recurrent macular detachment (1 with silicone oil underfill; 2 with proliferative vitreoretinopathy). The macula was attached in all eyes at last follow-up. Reattachment of the peripheral retina was achieved in 10 of 12 eyes. There were no anterior segment complications. CONCLUSIONS: Clear lens extraction with IOL placement during repair of retinal detachment with silicone oil tamponade does not seem to increase complications and may improve long-term visual rehabilitation, improve retinitis management by allowing better posterior segment visualization throughout the postoperative course, and decrease overall cost and morbidity associated with cataract extraction as a second procedure.