Michael Rauser

Retinal pigment epithelial tears after intravitreal bevacizumab injection for neovascular age-related macular degeneration.

Purpose: To study retinal pigment epithelium (RPE) tears after off-label intravitreal bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) injection for neovascular age-related macular degeneration. Eyes with a vascularized pigment epithelial detachment (PED) that developed an RPE tear were compared with eyes with a vascularized PED but without an RPE tear. Methods: Nine retina specialists across the United States and in Europe participated in this retrospective case series. All eyes that received intravitreal bevacizumab injection for choroidal neovascularization (CNV) over 12 months (October 2005 to September 2006) were included. Eyes without all three confirmed tests (fluorescein angiography, fundus photography, and optical coherence tomography) were excluded from analysis. Statistical analyses were performed on multiple characteristics of eyes with a vascularized PED that did and did not develop an RPE tear. Results: Among 2,785 intravitreal bevacizumab injections for 1,064 eyes, RPE tears were found in 22 eyes in 22 patients (2.2%). A vascularized PED was present in 21 of 22 eyes that developed an RPE tear (17.1% of PED eyes; 15, 100% occult CNV; 6, predominantly occult CNV). Mean interval from bevacizumab injections to RPE tears was 37.3 days. Mean follow-up time was 124.9 days. Mean subfoveal PED size was larger for eyes with tears than for those without tears (13.97 mm2 vs 9.9 mm2, respectively; P = 0.01; odds ratio, 1.09). There was substantially smaller mean ratio of CNV size to PED size for eyes with tears than for those without tears (27.9% vs 67.6%, respectively; P = 0.005). Mean pre–bevacizumab injection best-corrected Snellen visual acuity was 20/162, and mean post–RPE tear best-corrected visual acuity was 20/160 (P = 0.48). Conclusion: Large PED size is a predictor for RPE tears, and a small ratio of CNV size to PED size (<50%) is more common in eyes with RPE tears. Vision may be preserved despite RPE tears.

Optical coherence tomography-measured pigment epithelial detachment height as a predictor for retinal pigment epithelial tears associated with intravitreal bevacizumab injections.

Purpose: The purpose was to study preinjection optical coherence tomography–related factors in age-related macular degeneration eyes with retinal pigment epithelial detachment (PED) that may predispose retinal pigment epithelial (RPE) tears associated with intravitreal bevacizumab injections. Methods: This multicenter retrospective case series involving 9 retina specialists and 7 centers investigated Stratus optical coherence tomography (Carl Zeiss Meditec, Dublin, CA) parameters in eyes with vascularized PED (vPED) from February 2006 to February 2007. Of the 1,280 eyes in 1,255 patients receiving 2,890 intravitreal injections, there were 125 eyes with vPED. For every vPED eye that developed an RPE tear (Group 1), 3 or more vPED eyes without RPE tears (Group 2) were randomly selected in each study center during the same time period for comparison. The primary outcome measure was PED height (&mgr;m), and the secondary measures included volume index (vPED height × surface area), total macular volume, subretinal fluid, cystoid macular edema, center-point thickness, central 1 mm, and pre- and postinjection best-corrected Snellen visual acuities. Results: Twenty-one vPED eyes in 21 patients among 125 vPED eyes (16.8% of all vPED eyes) developed RPE tears. The 21 Group 1 eyes were compared with the 78 randomly selected Group 2 eyes. The vPED height was significantly higher for Group 1 eyes in comparison to Group 2 eyes (mean: 648.9 ± 245.0 vs. 338.1 ± 201.6 &mgr;m, P < 0.001). The same was true for the following: volume index (P = 0.001), subretinal fluid (P = 0.002), and total macular volume (P = 0.04). The mean preinjection and post-RPE tear best-corrected visual acuity were 0.92 logMAR (20/166) and 0.84 logMAR (20/137), respectively (P = 0.25). Multivariate analysis showed PED height to be the only significant risk factor associated with RPE tears in Group 1 eyes [odds ratio = 0.995 (95% confidence interval: 0.992–0.997), P < 0.001]. Conclusion: Elevated preinjection vPED height is the single most significant predictor for RPE tears after bevacizumab injections for vPED eyes. A vPED height >400 &mgr;m is associated with a significant risk for such a complication.

Macular edema after cataract surgery in eyes without preoperative central-involved diabetic macular edema.

IMPORTANCE The incidence of development or worsening of macular edema (ME) is variable in eyes without diabetic ME (DME) undergoing cataract surgery. OBJECTIVE To estimate the incidence of central-involved ME 16 weeks following cataract surgery in eyes with diabetic retinopathy without definite central-involved DME preoperatively. DESIGN, SETTING, AND PARTICIPANTS In a multicenter, prospective, observational study, 293 participants with diabetic retinopathy without definite central subfield thickening on optical coherence tomography (OCT) underwent cataract surgery. EXPOSURE Cataract extraction surgery performed within 28 days of enrollment of eyes without DME in individuals with diabetes mellitus. MAIN OUTCOMES AND MEASURES Development of central-involved ME defined as the following: (1) OCT central subfield thickness of 250 μm or greater (time-domain OCT) or 310 μm or greater (spectral-domain OCT) with at least a 1-step increase in logOCT central subfield thickness preoperatively to the 16-week visit; (2) at least a 2-step increase in logOCT central subfield thickness preoperatively to the 16-week visit; or (3) nontopical treatment for ME received before the 16-week visit with either of the OCT criteria met at the time of treatment. RESULTS The median participant age was 65 years. The median visual acuity letter score was 69 letters (Snellen equivalent 20/40). Forty-four percent of eyes had a history of treatment for DME. Sixteen weeks postoperatively, central-involved ME was noted in 0% (95% CI, 0%-20%) of 17 eyes with no preoperative DME. Of eyes with non-central-involved DME, 10% (95% CI, 5%-18%) of 97 eyes without central-involved DME and 12% (95% CI, 7%-19%) of 147 eyes with possible central-involved DME at baseline progressed to central-involved ME. History of DME treatment was significantly associated with central-involved ME development (P < .001). CONCLUSIONS AND RELEVANCE In eyes with diabetic retinopathy without concurrent central-involved DME, presence of non-central-involved DME immediately prior to cataract surgery or history of DME treatment may increase the risk of developing central-involved ME 16 weeks after cataract extraction.

Persistent Macular Thickening After Ranibizumab Treatment for Diabetic Macular Edema With Vision Impairment

IMPORTANCE The prevalence of persistent diabetic macular edema (DME) after months of anti-vascular endothelial growth factor therapy and its effect on visual acuity are unknown. OBJECTIVE To assess subsequent outcomes of eyes with DME persisting for 24 weeks after initiating treatment with 0.5 mg of ranibizumab. DESIGN, SETTING, AND PARTICIPANTS We performed post hoc, exploratory analyses of a randomized clinical trial from March 20, 2007, through January 29, 2014, from 117 of 296 eyes (39.5%) randomly assigned to receive ranibizumab with persistent DME (central subfield thickness ≥250 μm on time domain optical coherence tomography) through the 24-week visit. INTERVENTIONS Four monthly intravitreous injections of ranibizumab and then as needed per protocol. MAIN OUTCOMES AND MEASURES Cumulative 3-year probabilities of chronic persistent DME (failure to achieve a central subfield thickness <250 μm and at least a 10% reduction from the 24-week visit on at least 2 consecutive study visits) determined by life-table analyses, and at least 10 letter (≥2 line) gain or loss of visual acuity among those eyes. RESULTS The probability of chronic persistent DME among eyes with persistent DME at the 24-week visit decreased from 100% at the 32-week visit to 81.1% (99% CI, 69.6%-88.6%), 55.8% (99% CI, 42.9%-66.9%), and 40.1% (99% CI, 27.4%-52.4%) at the 1-, 2-, and 3-year visits, respectively. At 3 years, visual acuity improved in eyes with and without chronic persistent DME through the follow-up period, respectively, by a mean of 7 letters and 13 letters from baseline. Among 40 eyes with chronic persistent edema through 3 years, 17 (42.5%) (99% CI, 23.1%-63.7%) gained 10 letters or more from baseline, whereas 5 (12.5%) (99% CI, 2.8%-31.5%) lost 10 letters or more from baseline. CONCLUSIONS AND RELEVANCE These data suggest less than half of eyes treated for DME with intravitreous ranibizumab have persistent central-involved DME through 24 weeks after initiating treatment. Among the 40% that then have chronic persistent central-involved DME through 3 years, longer-term visual acuity outcomes appear to be slightly worse than in the 60% in which DME does not persist. Nevertheless, when following the treatment protocol used in this trial among eyes with vision impairment from DME, long-term improvement in visual acuity from baseline is typical and substantial (≥2-line) loss of visual acuity is likely uncommon through 3 years, even when central-involved DME chronically persists.

Recent clinical experience with famciclovir--a "third generation" nucleoside prodrug.

The herpesviruses continue to produce considerable morbidity in man. Once infected with herpes simplex (HSV), the virus remains dormant within the nervous system and may reactivate if provoked by stress, trauma and/or other factors. To date, there is no cure, but antiviral medication can reduce duration and severity of symptoms and prophylaxis can suppress recurrent episodes of disease. The second-generation guanosine nucleosides, acyclovir and penciclovir, are effective inhibitors with low toxicity; both, however, have relatively low oral bioavailability. Subsequently, the orally bioavailable prodrugs valaciclovir and famciclovir have been introduced. These compounds offer high oral bioavailabilty and deliver acyclovir and penciclovir, respectively, to the target cells by means of more convenient dosing schedules. This short review points to recent experience with famciclovir in the management of HSV and varicella-zoster virus.

Pupil dilation using a standard cataract surgery regimen alone or with atropine 1.0% pretreatment: Prospective comparative evaluation

PURPOSE: To compare the amount of pupil dilation produced by a set of commonly used preoperative mydriatic agents for cataract surgery, with the same regimen preceded by topical administration of atropine 1.0%. SETTING: Department of Ophthalmology, Loma Linda University, Loma Linda, California, USA. METHODS: In this prospective unmasked study, the baseline pupil size in eyes of volunteers was measured. Pupil size was then measured 30 minutes after instillation of the institutions standard dilation regimen for cataract surgery, which included phenylephrine 2.5%, tropicamide 1.0%, and cyclopentolate 1.0%. Several days later, the subjects returned for repeat measurements after pretreating the study eye(s) with atropine 1.0% 3 times a day the day previously and once on the morning of repeat dilation and measurements. Pupil size was again measured after administration of the standard regimen. RESULTS: The study included 72 eyes of 54 patients. A paired t test showed a statistically significant difference in mean pupil dilation between the standard regimen alone and the standard regimen with atropine 1.0% pretreatment. The mean pupil dilation was 7.3 mm ± 1.2 (SD) with the standard regimen alone and 6.9 ± 1.2 mm with the standard regimen with atropine pretreatment; the difference was statistically significant (P<.001). CONCLUSION: The addition of atropine 1.0% 1 day before administration of a standard preoperative dilating regimen for cataract surgery resulted in a smaller dilated pupil diameter than administration of the standard set of preoperative mydriatic agents alone. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Optical Coherence Tomography in Pediatric Ophthalmology: Current Roles and Future Directions

The application of existing optical coherence tomography (OCT) technology to the pediatric population is limited in both the design specification of the device and its hardware. However, the potential of OCT in the pediatric population has not been fully realized. The authors review the literature, highlighting the currently available spectral-domain OCT technology and summarizing the reported normal pediatric OCT parameters for retinal nerve fiber layer and macular thickness. They also review the pediatric ophthalmological conditions in which OCT has been used and discuss advancements in OCT design and their potential applications to the pediatric population. The use of OCT in pediatric populations is likely to increase greatly in the coming years, aiding clinical decision-making and providing new insights into pediatric disease pathophysiology.

Emerging therapies for herpes viral infections (types 1 - 8).

There are eight members of the herpesviridae family: herpes simplex virus-1 (HSV-1), HSV-2, varicella-zoster virus, Epstein–Barr virus, cytomegalovirus, human herpes virus-6, human herpes virus-7 and human herpes virus-8. The diseases caused by viruses of the herpesviridae family are treated with and managed by systemic and topical antiviral therapies and immunomodulating drugs. Because these viruses establish a latent state in hosts, antiherpetic agents, such as nucleoside analogues, only control symptoms of disease or prevent outbreaks, and cannot cure the infections. There is a need for treatments that require less frequent dosing, can be taken even when lesions are more advanced than the first signs or symptoms, and can treat resistant strains of the viruses without the toxicities of existing therapies. Immunomodulating agents, such as resiquimod, can act on the viruses indirectly by inducing host production of cytokines, and can thereby reduce recurrences of herpes. The new helicase primase inhibitors, which are the first non-nucleoside antiviral compounds, are being investigated for treatment of HSV disease, including infections resistant to existing therapy.

Renal cell carcinoma metastasis to the ciliary body responds to proton beam radiotherapy: a case report

IntroductionWe report an unexpected presentation of metastatic renal cell carcinoma (RCC) to the ciliary body and an interesting response to proton beam radiotherapy.Case presentationWe encountered a case of angle-closure glaucoma as the initial presentation of ocular metastasis to the ciliary body in a 65-year-old Caucasian man who had undergone right radical nephrectomy for RCC 15 years earlier. He underwent YAG (yttrium aluminium garnet) laser peripheral iridotomy while further metastatic workup took place. His condition was eventually diagnosed as stage IV metastatic RCC of the clear cell type and involved multiple sites, including the ciliary body, brain, lungs, liver, and pancreas. The progression of RCC metastasis to the ciliary body was studied for 16 months. The ciliary body mass continued to grow despite systemic treatment with temsirolimus and interleukin-2 and intravitreal injections of bevacizumab. The tumor size peaked at 6.11 × 6.06 mm before the start of proton therapy, which reduced the tumor size to 5.07 × 4.39 mm.ConclusionsRCC can produce metastases involving unusual sites many years after resection of the primary tumor. Proton therapy was found to be effective in treating RCC metastasis to the ciliary body in settings in which other treatment modalities failed.

Oxygen saturation in premature infants at risk for threshold retinopathy of prematurity.

Purpose We aimed to determine if oxygen saturation, desaturations, and saturation variability play a role in progression of retinopathy of prematurity (ROP) and need for laser treatment. Methods This was a retrospective case-control study. We performed chart review of premature infants in a university hospital neonatal intensive care unit consecutively examined for ROP between May 2000 and December 2001. We compared birthweight, postmenstrual age, and oxygen saturation for 3 weeks before laser treatment for threshold ROP in group 1 (n=19) (average weight at treatment 2508 grams) and group 2 (n=18) before they reached 2500 grams. Outcome measures were retinopathy progression and need for treatment. Results Adjusting for birthweight and postmenstrual age, known predictors of ROP progression, we found that babies requiring laser treatment (group 1) had lower average daily oxygen saturation levels in the study period, significantly on 5/20 days (25%). These babies had saturations below 95% on 18/20 days (90%). Babies not requiring laser (group 2) had saturations below 95% on 2/20 days (10%). The last day on which pretreatment saturations differed significantly was 2 days before laser. Group 1 had more desaturations below 80% (6.0±3.2) than group 2 (3.2±1.2), p=0.0002 (independent samples t tests). Saturations varied more for individual group 1 infants. Conclusions Decreased oxygen saturation as early as 3 weeks and as late as 2 days before laser, increased number of desaturations, and saturation variability were seen in babies eventually requiring laser treatment for ROP.