Severe Spontaneous Tilt of Scleral-Fixated Intraocular Lenses.

PURPOSE: To report and evaluate a multicenter series of 18 cases of severe, spontaneous IOL tilt involving the flanged intrascleral haptic fixation technique (FISHF). DESIGN: Clinical study with historical controls. METHODS: We report a cross-sectional study of 46 FISHF cases using the CT Lucia 602 IOL at a single academic center over a period of 24 weeks to determine the incidence of severe rotisserie-style rotational tilt. These rates were then compared with the same time-frame the prior year to help determine if this is a new phenomenon. Additional cases of severe tilt were solicited from another 4 academic centers. RESULTS: Among 46 FISHF cases at a single center, 5 developed severe tilt. No clear pattern in surgical technique, ocular history, or ocular anatomy was evident in these cases compared with controls, although the involved IOLs clustered within a narrow diopter range, indicative of a batch effect. In the same 24-week interval the year before, 33 FISHF cases were performed, none of which exhibited severe rotational tilt. In our multicenter dataset, 18 cases of tilt were identified. Surgeons included fellow and early-career physicians as well as surgeons with multiple years of experience with the Yamane technique. A variety of surgical approaches for FISHF were represented. In at least 8 of the cases, haptic rotation and/or dehiscence at the optic-haptic junction were documented. CONCLUSIONS: The identification of haptic rotation and dehiscence intraoperatively in several cases may reflect a new stability issue involving the optic-haptic junction.

Intraretinal pigmented cells in retinal degenerative disease.

PURPOSE: Invasion of pigmented cells into the retina occurs in retinal degenerative diseases, such as macular telangiectasia type 2 (MacTel) and retinitis pigmentosa (RP). These intraretinal pigmented cells may be derived from the retinal pigment epithelium (RPE), but differences and similarities between intraretinal pigmented cells and RPE have so far not been well characterised.Clinicopathologic case report. METHOD: Here, we compared intraretinal pigment cells with RPE cells by immunohistochemistry. Immunohistological stains for classic RPE markers (RPE65, CRALBP and KRT18) and blood vessel markers (lectin and collagen 4) were done on sections from postmortem eye tissue from two MacTel donors, an RP donor and a control donor. MAIN OUTCOME MEASURES: Presence of specific immunohistochemistry markers on intraretinal pigmented and RPE cells. RESULTS: We found that intraretinal pigmented cells did not express RPE65 and CRALBP, with a small subset expressing them weakly. However, they all expressed KRT18, which was also present in normal RPE cells. Interestingly, we also found clusters of KRT18-positive cells in the retina that were not pigmented. CONCLUSIONS: Our findings suggest that RPE cells invading the retina dedifferentiate (losing classic RPE markers) and can be pigmented or unpigmented. Therefore, the number of RPE cells invading the retina in retinal degenerative disease may be underappreciated by funduscopy.

Novel TMEM98, MFRP, PRSS56 variants in a large United States high hyperopia and nanophthalmos cohort.

Nanophthalmos is a rare condition defined by a small, structurally normal eye with resultant high hyperopia. While six genes have been implicated in this hereditary condition (MFRP, PRSS56, MYRF, TMEM98, CRB1,VMD2/BEST1), the relative contribution of these to nanophthalmos or to less severe high hyperopia (≥ + 5.50 spherical equivalent) has not been fully elucidated. We collected probands and families (n = 56) with high hyperopia or nanophthalmos (≤ 21.0 mm axial length). Of 53 families that passed quality control, plausible genetic diagnoses were identified in 10/53 (18.8%) by high-throughput panel or pooled exome sequencing. These include 1 TMEM98 family (1.9%), 5 MFRP families (9.4%), and 4 PRSS56 families (7.5%), with 4 additional families having single allelic hits in MFRP or PRSS56 (7.5%). A novel deleterious TMEM98 variant (NM_015544.3, c.602G>C, p.(Arg201Pro)) segregated with disease in 4 affected members of a family. Multiple novel missense and frameshift variants in MFRP and PRSS56 were identified. PRSS56 families were more likely to have choroidal folds than other solved families, while MFRP families were more likely to have retinal degeneration. Together, this study defines the prevalence of nanophthalmos gene variants in high hyperopia and nanophthalmos and indicates that a large fraction of cases remain outside of single gene coding sequences.

Maculopathy in Patients with Monoclonal Gammopathy of Undetermined Significance.

PURPOSE: To describe clinical findings, laboratory values, and treatment response of patients with monoclonal gammopathy of undetermined significance (MGUS) demonstrating neurosensory macular detachment. DESIGN: Retrospective case series. PARTICIPANTS: Seven eyes of 4 patients (3 men and 1 woman; age range, 60-81 years) with neurosensory macular detachment, treatment-resistant submacular fluid, and vitelliform material. METHODS: We retrospectively reviewed the medical and ocular histories, ocular examination findings, retinal imaging, ocular disease course, and laboratory findings in 4 patients with submacular fluid associated with MGUS. MAIN OUTCOME MEASURES: Description of the macular findings and treatment courses of 4 patients diagnosed with MGUS maculopathy. RESULTS: Seven eyes of 4 patients demonstrated neurosensory macular detachment with treatment-resistant submacular fluid and vitelliform material. No eyes demonstrated signs of significant hyperviscosity retinopathy. Fluorescein angiography showed no definite leakage in any involved eye. Laboratory evaluation revealed immunoglobulin G MGUS in all 4 patients. All 4 patients were resistant to treatments aimed at resolving the subretinal fluid, including some combination of anti-vascular endothelial growth factor injections, photodynamic therapy, topical dorzolamide, oral dosing of eplerenone or acetazolamide, or some combination thereof. In 3 patients, MGUS underwent malignant transformation 24 to 144 months after diagnosis, in 1 patient to lymphoplasmacytic lymphoma and in 2 patients to multiple myeloma. The fourth patient showed no evidence of malignancy 8 years after diagnosis. CONCLUSIONS: Submacular fluid without fluorescein leakage and unresponsive to conventional treatment may suggest an underlying immunoproliferative disorder that we have termed monoclonal gammopathy of macular significance. Given the propensity for monoclonal gammopathy of macular significance to transform into malignant disease in our series, serum protein analysis should be considered in patients with neurosensory macular detachment not attributable to known causes.

FUNDUS-WIDE SUBRETINAL AND PIGMENT EPITHELIAL ABNORMALITIES IN MACULAR TELANGIECTASIA TYPE 2.

PURPOSE: Macular telangiectasia Type 2 (MacTel) causes glial and photoreceptor cell death in a small, oval patch in the central retina. Beyond this oval area, no disease manifestations have been described so far. Here, we describe a novel pathological aspect of MacTel in the retinal pigment epithelium (RPE) that is not restricted to the clinically affected area but covers the entire retina. METHODS: We have studied postmortem eyes from four patients with MacTel by immunohistochemistry and electron microscopy. RESULTS: We found cellular debris in the subretinal space (between photoreceptor outer segments and RPE), consisting mainly of outer segments and RPE components. In healthy eyes, the RPE normally phagocytoses the tips of the continuously growing outer segments, a process considered to be essential for photoreceptor survival. However, in the patients with MacTel, we found no evidence of ongoing outer segment phagocytosis, and the apical surface of the RPE appeared abnormal throughout most of the retina. CONCLUSION: Reduced outer segment phagocytosis may explain the accumulating debris in the subretinal space but is a surprising finding because visual function in the peripheral retina is normal in patients with MacTel. Nevertheless, the subclinical pathology might induce a specific stress to which the central area is uniquely susceptible.

PATHOGENESIS OF PERSISTENT PLACOID MACULOPATHY: A Multimodal Imaging Analysis.

PURPOSE: To describe previously unreported clinical characteristics of persistent placoid maculopathy, suggest a pathogenesis of persistent placoid maculopathy using multimodal imaging, and provide evidence supporting high-dose immunosuppression for short-term management. METHODS: Retrospective case series. RESULTS: The cohort included 3 men with ages ranging from 55 years to 68 years. Persistent placoid maculopathy was bilateral in all 3 patients and characterized by recurrence and choroidal neovascularization in 1 patient. The median time to presentation was 3 months (range, 2-24 months), and follow-up was 8 months (range, 3-24 months). Previously unreported findings of far-peripheral lesions and optic nerve hyperfluorescence on fluorescein angiography were noted in separate individuals. In addition, findings from multimodal imaging supported an inflammatory pathogenesis of the inner choroid and the outer retina. Finally, all patients experienced substantial improvement to structural and functional measures in at least one eye within days to weeks of initiating high-dose corticosteroids (0.75-1 mg/kg/day). CONCLUSION: Multimodal imaging suggests that persistent placoid maculopathy has an inflammatory pathogenesis that may affect the inner choroid with secondary changes to the retinal pigment epithelium and the outer retina. High-dose corticosteroids may provide short-term benefit.

Fully automated detection of diabetic macular edema and dry age-related macular degeneration from optical coherence tomography images.

We present a novel fully automated algorithm for the detection of retinal diseases via optical coherence tomography (OCT) imaging. Our algorithm utilizes multiscale histograms of oriented gradient descriptors as feature vectors of a support vector machine based classifier. The spectral domain OCT data sets used for cross-validation consisted of volumetric scans acquired from 45 subjects: 15 normal subjects, 15 patients with dry age-related macular degeneration (AMD), and 15 patients with diabetic macular edema (DME). Our classifier correctly identified 100% of cases with AMD, 100% cases with DME, and 86.67% cases of normal subjects. This algorithm is a potentially impactful tool for the remote diagnosis of ophthalmic diseases.

Use of intravitreal rituximab for treatment of vitreoretinal lymphoma.

AIM: Vitreoretinal lymphoma is a diffuse large B cell non-Hodgkin lymphoma. Targeting malignant cells with rituximab is being used increasingly as local chemotherapy, but information on this treatment is scant. We aimed to describe current therapeutic approaches, as well as responses to and complications of, intravitreal rituximab in patients with vitreoretinal lymphoma. METHODS: Clinical data were collected in a standardised manner retrospectively on patients with vitreoretinal lymphoma treated with intravitreal rituximab. RESULTS: 48 eyes (34 patients) with vitreoretinal lymphoma were treated with a median of 3.5 intravitreal injections of rituximab (1 mg/0.1 mL) for new diagnosis (68.8%), progressive disease (29.9%) and maintenance therapy (2.1%). Intravitreal rituximab±methotrexate was the sole treatment in 19 eyes (39.6%). 31 eyes (64.6%) eyes achieved complete remission, after a median of 3 injections; 7 of these eyes developed recurrent disease. 11 eyes (22.9%) achieved partial remission. Although rituximab may have contributed to complications reported in 12 eyes (25.0%), a 2-line loss of Snellen visual acuity occurred in only 2 of those eyes (4.2%). CONCLUSIONS: Approaches in rituximab-based intravitreal chemotherapy vary widely, but our findings suggest that this treatment may be safe and effective in inducing remission in a majority of eyes with vitreoretinal lymphoma.

Quantification of fundus autofluorescence to detect disease severity in nonexudative age-related macular degeneration.

IMPORTANCE: Accurate assessment of disease burden and determination of disease progression are challenging in dry age-related macular degeneration (AMD). We assessed the utility of quantified fundus autofluorescence in (FAF) the evaluation and follow-up of dry AMD. OBJECTIVE: To develop a method for quantitative FAF image analysis that is capable of stratifying severity of nonexudative AMD. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis from 2008 to 2012 at a university eye center of FAF images taken of normal and nonexudative AMD eyes compared the Index of Retinal Autofluorescence (IRA) with retinal specialists' clinical rankings of FAF images and the Age-Related Eye Disease Study (AREDS) grading scheme of corresponding color fundus photographs. INTERVENTION: Digital files of Heidelberg Spectralis FAF images taken of normal and nonexudative AMD eyes were analyzed. For each image, a unique horizontally oriented FAF signature composed of vertically averaged gray-scale values was generated through the fovea. A pairwise comparison of 2 signatures was performed using a modified difference of squares method, which generated a single quantitative value, the IRA. MAIN OUTCOMES AND MEASURES: The effects of intersession testing, cataract extraction, pupillary dilation, focal plane, and gain settings on the IRA were assessed. RESULTS: The FAF images taken of the same subjects at different times demonstrated low intersession variability of the IRA (intraclass coefficient = 0.75; 95% CI, 0.45-0.92). The IRA was affected by cataract severity, cataract extraction, small pupillary diameters (<5.5 mm), defocusing, and excessive high or low camera gain. The IRA values correlated with both subjective clinical rankings by retinal specialists (r(s) = 0.77). The IRA was positively correlated with AREDS score (r(s) = 0.73) and could statistically distinguish AREDS grades 3 and 4 (P < .001). Serial imaging demonstrated the utility of the method for identifying clinically meaningful disease progression. CONCLUSIONS AND RELEVANCE: The IRA method applied to FAF digital files can quantify AMD disease severity and may be helpful in identifying AMD progression.

A longitudinal analysis of risk factors associated with central retinal vein occlusion.

PURPOSE: To identify risk factors associated with central retinal vein occlusion (CRVO) among a diverse group of patients throughout the United States. DESIGN: Longitudinal cohort study. PARTICIPANTS: All beneficiaries aged ≥ 55 years who were continuously enrolled in a managed care network for at least 2 years and who had ≥ 2 visits to an eye care provider from 2001 to 2009. METHODS: Insurance billing codes were used to identify individuals with a newly diagnosed CRVO. Multivariable Cox regression was performed to determine the factors associated with CRVO development. MAIN OUTCOME MEASURES: Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of being diagnosed with CRVO. RESULTS: Of the 494 165 enrollees who met the study inclusion criteria, 1302 (0.26%) were diagnosed with CRVO over 5.4 (± 1.8) years. After adjustment for known confounders, blacks had a 58% increased risk of CRVO compared with whites (HR, 1.58; 95% CI, 1.25-1.99), and women had a 25% decreased risk of CRVO compared with men (HR, 0.75; 95% CI, 0.66-0.85). A diagnosis of stroke increased the hazard of CRVO by 44% (HR, 1.44; 95% CI, 1.23-1.68), and hypercoagulable state was associated with a 145% increased CRVO risk (HR, 2.45; 95% CI, 1.40-4.28). Individuals with end-organ damage from hypertension (HTN) or diabetes mellitus (DM) had a 92% (HR, 1.92; 95% CI, 1.52-2.42) and 53% (HR, 1.53; 95% CI, 1.28-1.84) increased risk of CRVO, respectively, relative to those without these conditions. CONCLUSIONS: This study confirms that HTN and vascular diseases are important risk factors for CRVO. We also identify black race as being associated with CRVO, which was not well appreciated previously. Furthermore, we show that compared with patients without DM, individuals with end-organ damage from DM have a heightened risk of CRVO, whereas those with uncomplicated DM are not at increased risk of CRVO. This finding may provide a potential explanation for the conflicting reports in the literature on the association between CRVO and DM. Information from analyses such as this can be used to create a risk calculator to identify possible individuals at greatest risk for CRVO.

Diffusion of technologies for the care of older adults with exudative age-related macular degeneration.

PURPOSE: To determine patterns of diffusion of diagnostic tests and therapeutic interventions in the United States through 2010 for patients with newly diagnosed exudative macular degeneration (AMD). DESIGN: Retrospective longitudinal cohort analysis. METHODS: SETTING AND PATIENT POPULATION: A total of 23 941 Medicare beneficiaries with exudative AMD newly diagnosed during 1992-2009. OBSERVATION PROCEDURES: Current Procedural Technology (CPT-4) billing codes were used to identify use of diagnostic tests (optical coherence tomography, fluorescein angiography, and fundus photography) and therapeutic interventions (argon laser photocoagulation, photodynamic therapy, intravitreal corticosteroids, and anti-vascular endothelial growth factor [VEGF] agents) used by these beneficiaries during the first year following diagnosis. MAIN OUTCOME MEASURES: Rates of use of study diagnostic and therapeutic procedures. RESULTS: Diffusion was rapid for each successive new diagnostic and treatment modality, with use of newer procedures quickly replacing existing ones. The number of beneficiaries treated with anti-VEGF agents for exudative AMD was considerably greater than for prior innovations, rising from use in 4.0% of beneficiaries in 2004-05 to 62.7% in 2009-10. In each year from first diagnosis years 2006-2009 and in different practice settings, use of bevacizumab exceeded that of ranibizumab (60%-78% vs 33%-47%, respectively). Rates of diffusion of the various therapies were relatively similar in communities throughout the United States irrespective of presence of a major teaching hospital in the vicinity. CONCLUSIONS: Newer, more effective therapeutic interventions for exudative AMD diffused rapidly throughout the United States, quickly replacing older, less effective interventions. Although improving patient outcomes, rapid diffusion raises important public policy issues for Medicare and other payers to consider.

Noninvasive imaging of mitochondrial dysfunction in dry age-related macular degeneration.

BACKGROUND AND OBJECTIVE: Oxidative stress and mitochondrial dysfunction are implicated in the pathogenesis of age-related macular degeneration (AMD). Because increased flavoprotein fluorescence (FPF) is indicative of mitochondrial dysfunction, the authors attempted to detect mitochondrial dysfunction in eyes with AMD using FPF. PATIENTS AND METHODS: Six nonexudative eyes with AMD, including three with geographic atrophy (GA), and age-matched control eyes were imaged with a FPF device. Qualitative and quantitative analyses were conducted on the FPF images. RESULTS: Five eyes with AMD, including all three eyes with GA, showed qualitative and/or quantitative FPF heterogeneity that was not present in control eyes. Mean FPF average intensities of eyes with AMD with (P = .044) and without (P = .00060) GA were significantly greater than those of control eyes. The standard deviations of FPF images were greater in eyes with AMD (P = .020). CONCLUSION: In this small cluster of patients with AMD, retinal FPF is increased, suggesting elevated mitochondrial dysfunction. FPF heterogeneity indicates that an increased variability in mitochondrial dysfunction seems to be present in eyes with advanced disease.

Successful salvage therapy of Fusarium endophthalmitis secondary to keratitis: an interventional case series.

PURPOSE: To describe a combination of treatment modalities used for the successful eradication of Fusarium endophthalmitis. DESIGN: Interventional case series. PARTICIPANTS: Three consecutive patients with keratitis-associated Fusarium endophthalmitis. METHODS: After failure of traditional management options, a combination of intravitreal and long-term, high-dose systemic voriconazole, topical antifungal medications, and surgical intervention, with penetrating keratoplasty, lensectomy, and endoscopic-guided pars plana vitrectomy, was administered to each patient. RESULTS: All three cases achieved full resolution of the infection, with a final Snellen visual acuity score of 20/50 to 20/70. CONCLUSIONS: An aggressive combination of therapeutic modalities, including the removal of subiris abscesses, might be needed for the successful resolution of Fusarium endophthalmitis.

Acute anterior uveitis following intravitreal bevacizumab but not subsequent ranibizumab.

PURPOSE: Previous reports have identified noninfectious uveitis as a potential sequela following both intravitreal bevacizumab and ranibizumab injections. We present two unique cases of acute anterior uveitis following intravitreal bevacizumab that did not occur with subsequent ranibizumab injections. METHODS: Case report. CONCLUSION: These cases may reflect differences in the etiology of anterior uveitis following intravitreal bevacizumab and ranibizumab. Given these differences, it may be reasonable to offer ranibizumab to patients who have experienced presumed bevacizumab-induced anterior uveitis.

Intravitreal daptomycin: a safety and efficacy study.

PURPOSE: To determine the ocular toxicity of intravitreally injected daptomycin, a novel antibiotic for treatment of vancomycin-resistant organisms, and its efficacy in treating intraocular infection with coagulase-negative Staphylococcus epidermidis. METHODS: Four doses of intravitreal daptomycin were injected (75, 188, 375, and 750 µg) into 1 eye of Dutch belted rabbits (n = 3 per dose). Clinical examination, electroretinography, and histologic analysis were performed preinjection and 2 weeks after injection and compared with the fellow eye that received only intravitreal balanced salt solution. Experimental S epidermidis endophthalmitis was induced in Dutch belted rabbits (n = 24), and the ability of 200 µg of intravitreal daptomycin to result in culture-negative vitreous samples was measured at 24 hours and 48 hours. RESULTS: Seventy-five micrograms and 188 µg of daptomycin demonstrated acceptable safety profiles when injected intravitreally in Dutch belted rabbits. There was a dose-dependent increase in cataract formation, electroretinogram suppression, and photoreceptor damage with higher doses. Two hundred micrograms of intravitreal daptomycin resulted in near-complete vitreous sterilization 24 hours after treatment. Vitreous sterilization was complete by 48 hours. CONCLUSION: A dose of 200 µg of intravitreal daptomycin appears to be safe and efficacious in a rabbit model of bacterial endophthalmitis. Future investigations should focus on daptomycin as a therapeutic option for treating intraocular infection caused by vancomycin-resistant organisms.

Treatment of endogenous fungal endophthalmitis: focus on new antifungal agents.

Endogenous fungal endophthalmitis, involving only the chorioretinal structures or extending to involve the vitreous (vitritis), is a sight-threatening infection requiring early appropriate therapy. Endophthalmitis is a relatively frequent complication of candidemia and less commonly occurs in patients who have invasive aspergillosis. Because the eye is a protected compartment, penetration of systemically administered antifungal agents is highly variable. In the posterior segment of the eye, amphotericin B (AmB) achieves very poor concentrations, but fluconazole concentrations are high. Among newer antifungal agents, voriconazole shows the most promise, because therapeutic concentrations for most Candida and Aspergillus species are achieved in the vitreous, and its antifungal activity is broad. In contrast, neither posaconazole nor the 3 echinocandins achieve adequate therapeutic concentrations in the vitreous. For sight-threatening macular involvement and vitritis, intravitreal injection of either AmB or voriconazole is helpful to achieve high local antifungal activity as quickly as possible. We review the available evidence regarding the most appropriate use of antifungal agents for endogenous fungal endophthalmitis, with the emphasis on treatment of infections due to Candida species.

Retinoblastoma in a 48-year-old woman.

PURPOSE: The purpose of this study was to describe an unusual presentation of retinoblastoma in an adult. METHODS: Retrospective case report. RESULTS: A 48-year-old woman with floaters was found to have an amelanotic intraocular mass with localized vitreous seeds in the superior fundus. Metastatic workup was negative. Cytologic examination of the vitrectomy specimen showed a malignant neoplasm with neuroendocrine differentiation, suspicious for carcinoid tumor. The patient later was found to have a lung lesion presumed to be a carcinoid tumor. She was treated with external beam radiation to the eye, but 1 year later, a new retinal tumor was discovered inferiorly requiring plaque radiotherapy. Soon thereafter, she developed massive intraocular recurrence. The eye was enucleated. Histopathology revealed small round blue cells with round hyperchromatic nuclei. Rosettes were also present within the tumor consistent with retinoblastoma. CONCLUSION: Late-onset retinoblastoma can occur in adults, and the diagnosis can be challenging.

High-resolution OCT imaging of RPE degeneration in bilateral diffuse uveal melanocytic proliferation.

Bilateral diffuse uveal melanocytic proliferation is a rare paraneoplastic syndrome that presents with bilateral progressive loss of vision. A 70-year-old woman presented with a 3-month history of progressive, bilateral vision loss. The patient had bilateral, diffuse, shallow, subretinal fluid with patchy, reddish-brown lesions at the level of the retinal pigment epithelium (RPE) that showed significant early hyperfluorescence on fluorescein angiography and a corresponding loss of autofluorescence. Optical coherence tomography of both eyes revealed complete RPE and inner segment/outer segment junction loss with adjacent areas of thickening at the level of the RPE. Bilateral diffuse uveal melanocytic proliferation was diagnosed based on these clinical findings, and a systemic evaluation for malignancy revealed metastatic endometrial adenocarcinoma. Both autofluorescence and optical coherence tomography demonstrated unique imaging characteristics that correlated with the reported histopathology of bilateral diffuse uveal melanocytic proliferation. These imaging modalities can contribute to the rapid and accurate diagnosis of bilateral diffuse uveal melanocytic proliferation.

Vitreous penetration of orally administered famciclovir.

PURPOSE: To determine the vitreous penetration of penciclovir (Denavir; GlaxoSmithKline, Philadelphia, Pennsylvania, USA) after oral administration of the prodrug famciclovir (Famvir; Novartis Pharmaceuticals Corp, East Hanover, New Jersey, USA). DESIGN: Prospective interventional case series. METHODS: Ten patients undergoing elective pars plana vitrectomy at a single institution were enrolled to take 3 oral doses of famciclovir 500 mg the day preceding surgery and a fourth dose on the morning of surgery. Blood and undiluted vitreous samples were acquired from each patient during surgery. High-performance liquid chromatography was used to determine the concentration of penciclovir in each sample. Exclusion criteria included prior vitrectomy, compromised blood-retina barrier, renal or hepatic disease, human immunodeficiency virus infection, bone marrow or renal transplantation, pregnancy or breastfeeding, history of adverse reaction or allergy to famciclovir or penciclovir, and antiviral, probenecid, or cimetidine use within 1 month of surgery. RESULTS: Ten eyes of 10 patients ranging in age from 26 to 82 were included. All patients had normal renal and hepatic function as determined by history and laboratory values. Mean serum penciclovir concentration +/- standard deviation was 4.45 +/- 1.31 microg/ml (range, 2.51 to 6.34 microg/ml). Mean vitreous penciclovir concentration was 1.21 +/- 0.38 microg/ml (range, 0.39 to 1.88 microg/ml). Mean vitreous-to-serum concentration ratio of penciclovir was 0.28 +/- 0.09 (range, 0.16 to 0.41). CONCLUSIONS: Oral administration of famciclovir results in vitreous concentrations of penciclovir within the inhibitory ranges for herpes simplex 1, herpes simplex 2, and varicella zoster virus. Oral famciclovir may be a reasonable alternative to intravenous acyclovir (Zovirax; GlaxoSmithKline) in the treatment of acute retinal necrosis, especially in cases of acyclovir resistance or patient inability to tolerate prolonged intravenous treatment.

Vitreous penetration of orally administered valacyclovir.

PURPOSE: To investigate the vitreous penetration of acyclovir, the active metabolite of valacyclovir, after oral administration of valacyclovir. DESIGN: Prospective, interventional case series. METHODS: Ten patients scheduled for elective pars plana vitrectomy at a single academic institution were given three oral doses of valacyclovir 1000 mg eight hours apart the day before surgery, with a fourth dose on the morning of surgery. Blood and undiluted vitreous samples were obtained during surgery and subsequently were analyzed with high-performance liquid chromatography to determine the concentrations of acyclovir present. RESULTS: Ten eyes of 10 subjects ranging in age from 46 to 83 years were included. All patients had normal renal and hepatic function as confirmed by metabolic panels obtained before surgery. Mean serum acyclovir concentration +/- standard deviation was 4.41 +/- 0.88 microg/ml (range, 3.18 to 5.92 microg/ml), mean vitreous acyclovir concentration was 1.03 +/- 0.23 microg/ml (range, 0.67 to 1.33 microg/ml), and mean vitreous-to-serum concentration ratio of acyclovir was 0.24 +/- 0.06 (range, 0.16 to 0.34). CONCLUSIONS: Orally administered valacyclovir results in substantial vitreous penetration of acyclovir. The vitreous concentrations achieved in noninflamed eyes are within the reported inhibitory ranges for most strains of herpes simplex 1, herpes simplex 2, and varicella zoster virus. This suggests that orally administered valacyclovir may be an alternative to intravenous acyclovir in the treatment of acute retinal necrosis.