Rajeev H. Muni

The benefits of steroids versus steroids plus antivirals for treatment of Bell’s palsy: a meta-analysis

Objective To determine whether steroids plus antivirals provide a better degree of facial muscle recovery in patients with Bell’s palsy than steroids alone. Design Meta-analysis. Data sources PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for studies published in all languages from 1984 to January 2009. Additional studies were identified from cited references. Selection criteria Randomised controlled trials that compared steroids with the combination of steroids and antivirals for the treatment of Bell’s palsy were included in this study. At least one month of follow-up and a primary end point of at least partial facial muscle recovery, as defined by a House-Brackmann grade of at least 2 (complete palsy is designated a grade of 6) or an equivalent score on an alternative recognised scoring system, were required. Review methods Two authors independently reviewed studies for methodological quality, treatment regimens, duration of symptoms before treatment, length of follow-up, and outcomes. Odds ratios with 95% confidence intervals were calculated and pooled using a random effects model. Results Six trials were included, a total of 1145 patients; 574 patients received steroids alone and 571 patients received steroids and antivirals. The pooled odds ratio for facial muscle recovery showed no benefit of steroids plus antivirals compared with steroids alone (odds ratio 1.50, 95% confidence interval 0.83 to 2.69; P=0.18). A one study removed analysis showed that the highest quality studies had the greatest effect on the lack of difference between study arms shown by the odds ratio. Subgroup analyses assessing causes of heterogeneity defined a priori (time from symptom onset to treatment, length of follow-up, and type of antiviral studied) showed no benefit of antivirals in addition to that provided by steroids. Conclusions Antivirals did not provide an added benefit in achieving at least partial facial muscle recovery compared with steroids alone in patients with Bell’s palsy. This study does not, therefore, support the routine use of antivirals in Bell’s palsy. Future studies should use improved herpes virus diagnostics and newer antivirals to assess whether combination therapy benefits patients with more severe facial paralysis at study entry.

Prospective Study of Inflammatory Biomarkers and Risk of Diabetic Retinopathy in the Diabetes Control and Complications Trial

IMPORTANCE This study demonstrates that increasing quintiles of baseline high-sensitivity C-reactive protein (hsCRP) level may be associated with higher risk of incident clinically significant macular edema, the leading cause of vision loss in working-aged individuals in North America. OBJECTIVE To determine whether baseline levels of hsCRP and intercellular adhesion molecule 1 (ICAM-1) predict development and progression of diabetic retinopathy (DR), clinically significant macular edema (CSME), retinal hard exudates, and proliferative DR in the Diabetes Control and Complications Trial (DCCT) cohort. DESIGN The DCCT was a large multicenter randomized controlled clinical trial. SETTING Twenty-nine medical centers in the United States and Canada. PARTICIPANTS The DCCT population consisted of 1441 subjects with type 1 diabetes mellitus aged 13 to 39 years at study entry. INTERVENTION We measured levels of hsCRP, ICAM-1, vascular cell adhesion molecule 1, and tumor necrosis factor α receptor 1 in stored baseline blood samples. MAIN OUTCOME MEASURES We assessed the association of levels of hsCRP, ICAM-1, vascular cell adhesion molecule 1, and tumor necrosis factor α receptor 1 with incident DR end points ascertained from grading of standardized 7-field stereoscopic retinal color photographs taken at baseline and every 6 months during follow-up. RESULTS After adjustment for randomized treatment assignment and other factors, we observed a statistically significant association between hsCRP and risk of CSME, with a relative risk (RR) for the top vs bottom quintile of 1.83 (95% CI, 0.94-3.55; P for trend = .01). Similarly, for the development of retinal hard exudates, the RR for the top vs bottom quintile of hsCRP level was 1.78 (95% CI, 0.98-3.25; P for trend = .004), whereas for ICAM-1 level, the RR comparing the top vs bottom quintiles was 1.50 (95% CI, 0.84-2.68; P for trend = .05). There were no statistically significant associations between baseline VCAM-1 or tumor necrosis factor α receptor 1 levels and risk of any of the DR end points. CONCLUSIONS AND RELEVANCE After adjusting for known risk factors, increasing quintiles of baseline hsCRP level may be associated with higher risk of incident CSME and macular hard exudate in the DCCT cohort. Circulating levels of ICAM-1 may also be associated with the development of retinal hard exudates.

Retinoschisis Detected With Handheld Spectral-Domain Optical Coherence Tomography in Neonates With Advanced Retinopathy of Prematurity

OBJECTIVES The recent development of handheld spectral-domain optical coherence tomography (HHSD-OCT) has enabled us to obtain high-resolution retinal scans of premature infants with retinopathy of prematurity (ROP). The purpose of this study is to document HHSD-OCT findings in laser-treated neonates with progressive ROP. METHODS This is a retrospective consecutive case series of 3 patients with progressive ROP despite laser photocoagulation. All patients were transferred from peripheral neonatal intensive care units (NICUs) to the Childrens Hospital Los Angeles. All patients had a complete ocular examination, fundus photography, fluorescein angiography, and HHSD-OCT. RESULTS All 3 patients had active progressive ROP despite prior laser photocoagulation. Of the 6 eyes, 1 was excluded from the study because it had an exudative retinal detachment following laser photocoagulation. Retinal detachment was not detected on clinical examination in the 5 remaining eyes, although there was vitreoretinal traction at the ridges of 3 of the 5 eyes. The HHSD-OCT identified presumed retinoschisis in all 5 study eyes. CONCLUSIONS Tractional retinoschisis may be an important finding in progressive laser-treated ROP, made possible by use of the HHSD-OCT. This finding may have significant implications for how we classify and treat patients whose ROP is progressing despite laser treatment. Furthermore, the use of the HHSD-OCT can provide valuable insight into the interaction of the retina, vitreous, and ridge in patients with progressive ROP, and it allows shallow detachments and retinoschisis to be diagnosed earlier and more accurately than would otherwise be possible.

Hand-held spectral domain optical coherence tomography finding in shaken-baby syndrome.

Purpose: The purpose of this study was to document the hand-held spectral domain optical coherence tomography (HHSD-OCT, Bioptigen, Durham, NC) findings in shaken-baby syndrome (SBS). The nonaccidental trauma in SBS has been associated with retinal findings, including hemorrhages in all layers of the retina and retinoschisis. Methods: Three consecutive patients with presumed SBS underwent complete ocular examination, fundus photography with the RetCam (Clarity Medical Systems, Pleasanton, CA), and imaging with the HHSD-OCT. Acquisition of the HHSD-OCT images required an assistant to stabilize the head of the infant. Results: All three patients had clinical findings consistent with SBS, including preretinal and intraretinal hemorrhages. Hand-held spectral domain optical coherence tomography documented focal posterior vitreous separation in four of the five eyes with multilayered retinoschisis in one eye, disruption of the foveal architecture and foveolar detachment in one eye, and disinsertion of the internal limiting membrane or inner retinoschisis in one eye. Hand-held spectral domain optical coherence tomography documented preretinal hemorrhages in all five eyes. Conclusion: Hand-held spectral domain optical coherence tomography is helpful in the evaluation of patients with SBS. All patients in our series had vitreoretinal abnormalities not detected on clinical examination, including, for example, multilayered retinoschisis. Hand-held spectral domain optical coherence tomography allows high-resolution imaging of the vitreoretinal interface and retina in infants with SBS and has provided insight into the mechanism of various retinal findings.

Effectiveness of intravitreal ranibizumab for the treatment of neovascular age-related macular degeneration in a Canadian retina practice: a retrospective review

OBJECTIVE To assess the effectiveness of intravitreal ranibizumab for neovascular age-related macular degeneration (AMD) in a tertiary care retina practice and compare these results with published efficacy data from randomized clinical trials. DESIGN Nonrandomized, consecutive, single-centre, retrospective chart review analysis. PARTICIPANTS Ninety-four patients (95 eyes) with neovascular AMD. METHODS All treatment-naïve patients with neovascular AMD who received ranibizumab and for whom 1 year of follow-up was available were included in the analysis. The following information was gathered from each patients chart: age, sex, ocular history, treated eye, duration of symptoms at presentation, subtype of choroidal neovascular membrane, Snellen visual acuity at each visit, number of injections, visits, and optical coherence tomography measurements. RESULTS Subjects had a mean age of 81 (SD 7.11) years. The mean number of injections was 5.1 (SD 2.85) with a mean of 9.4 (SD 2.27) visits in the 12-month period. Overall, there was a gain of 2.88 (SD 24.6) letters in all eyes, and a loss of 2.5 (SD 23.1) letters in patients who met the visual acuity inclusion criteria for the clinical trials. Of the patients who met the inclusion criteria, 75% lost fewer than 15 letters and 11% gained more than 15 letters. CONCLUSIONS Visual outcomes in our study patients compared poorly with the clinical trials. Possibilities for the disparity include gaps in the number and frequency of follow-up visits, patient or doctor assessment fatigue, or gaps in optical coherence tomography utilization and the number of injections administered.

Management of pediatric choroidal neovascular membranes with intravitreal anti-VEGF agents: a retrospective consecutive case series

OBJECTIVE To report the results of pediatric choroidal neovascular membranes (CNVMs) secondary to a variety of etiologies treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents. DESIGN Retrospective case series. PARTICIPANTS Four pediatric patients at the Hosptial for Sick Children with CNVMs secondary to a variety of etiologies. METHODS Each patient received multiple treatments with one of the following anti-VEGF agents: pegaptanib sodium, bevacizumab, or ranibizumab. Progress was monitored by clinical exam, optical coherence tomography (OCT), and fluorescein angiography. RESULTS The mean age of our patients was 11.5 years (range, 8-15 years). Patients were followed for a mean of 10 months (range, 4-14 months). One patient was treated with pegaptanib sodium, 2 with bevacizumab, and 1 with ranibizumab. Following treatment, 1 patient showed an improvement and 3 showed stabilization of vision with reduction of fluid on clinical exam and OCT, and cessation of leakage on the fluorescein angiogram. Patients required 2-5 injections of the anti-VEGF agent. No ocular or systemic adverse events were observed in any of our treated patients. CONCLUSIONS Anti-VEGF agents were effective in the treatment of pediatric CNVMs in this case series. However, we do not know how these results would have differed from other treatment modalities, including observation. We did not observe any adverse side effects; however, larger studies are required to document the safety of these medications in the pediatric population where normal angiogenesis is occurring.

Real-time evaluation of diffusion of the local anesthetic solution during peribulbar block using ultrasound imaging and clinical correlates of diffusion

Background and Objectives The aims of this prospective observational study were to assess the incidence of intraconal spread during peribulbar (extraconal) anesthesia by real-time ultrasound imaging of the retro-orbital compartment and to determine whether a complete sensory and motor block (with akinesia) of the eye is directly related to the intraconal spread. Methods Ultrasound imaging was performed in 100 patients who underwent a surgical procedure on the posterior segment of the eye. All patients received a peribulbar block using the inferolateral approach. Once the needle was in place, a linear ultrasound transducer was placed over the eyelid and the spread of local anesthetics was assessed during the injection (real time). Akinesia was assessed by a blinded observer 10 minutes after block placement. The incidence of intraconal spread and its correlation with a complete akinesia was measured. Results The overall block failure rate was 28% in terms of akinesia, and the rate of rescue blocks was 20%. Clear intraconal spread during injection of the local anesthetic mixture could be detected with ultrasound imaging in 61 of 100 patients. The positive predictive value for successful block when intraconal spread was detected was 98% (95% confidence interval, 91%-100%). The association between clear and no evidence of intraconal spread and effective block was statistically significant (&khgr;2 test, P < 0.001). Conclusions Ultrasound imaging provides information of local anesthetic spread within the retro-orbital space, which might assist in the prediction of block success.

Effectiveness at 1 year of monthly versus variable-dosing intravitreal ranibizumab in the treatment of choroidal neovascularization secondary to age-related macular degeneration.

Purpose To evaluate the visual acuity results of monthly ranibizumab injections compared with a variable-dosing schedule for the treatment of neovascular age-related macular degeneration. Methods A retrospective study that compared two cohorts of consecutive patients. All patients were treatment naive, with baseline visual acuity of 20/400 or better, and completed 12 months of therapy. In the first group all patients received monthly injections. In the other group, after 3 monthly loading doses, a variable-dosing schedule was used, based on a monthly clinical assessment and optical coherence tomography. Results Fifty-six consecutive patients (60 eyes) were included. At 12 months the median number of injections were 12 and 8, respectively, and the mean change in Snellen visual acuity was an improvement of 0.27 logarithm of the minimum angle of resolution in the monthly treated group versus 0.21 logarithm of the minimum angle of resolution improvement in the variable-dosing group (P = 0.53). In the monthly treated group 96.8% of eyes lost <0.3 logarithm of the minimum angle of resolution versus 96.6% of eyes in the variable-dosing group (P = 1.0). Conclusion We were able to show that in our clinical setting patients achieved similar visual acuity results with either monthly injections or with a variable-dosing protocol. There was a trend toward better results with monthly treatment.

AQUEOUS HUMOR CYTOKINE LEVELS AS BIOMARKERS OF DISEASE SEVERITY IN DIABETIC MACULAR EDEMA.

Purpose: To determine whether aqueous cytokine levels correlate with disease severity in diabetic macular edema. Methods: A prospective cross-sectional study of 49 adults with diabetes mellitus, centre-involving diabetic macular edema and central subfield macular thickness ≥310 &mgr;m on spectral domain optical coherence tomography. Clinical examination and aqueous sampling were carried out before an initial injection of ranibizumab. Multiplex immunoassay of sample was carried out for vascular endothelial growth factor, placental growth factor, transforming growth factor beta, intercellular adhesion molecule-1, interleukin (IL)-2, IL-3, IL-6, IL-8, IL-10, IL-17, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, and epidermal growth factor. Multivariate robust regression models were constructed, and adjusted for age, lens status, or severity of retinopathy, and size of foveal avascular zone. Results: Spectral domain optical coherence tomography macular volume was an excellent measure of disease severity, correlating strongly with central subfield macular thickness (P < 0.001), best-corrected Snellen visual acuity (P < 0.001), and baseline diabetic retinopathy severity (P = 0.01). Elevated aqueous intercellular adhesion molecule-1 correlated with greater macular volume (P = 0.002). No aqueous cytokine, including VEGF, correlated with central subfield macular thickness. There was an association between IL-10 levels and best-corrected Snellen visual acuity (P = 0.03). Conclusion: Aqueous intercellular adhesion molecule-1 correlates with disease severity as measured by macular volume on spectral domain optical coherence tomography, and IL-10 is associated with BCVA. Intercellular adhesion molecule-1 may be a clinically useful biomarker for diabetic macular edema severity.

Post-traumatic vancomycin-resistant enterococcal endophthalmitis

The emergence of antibiotic-resistant organisms among severe ocular infections is of grave concern. We describe the first reported case of vancomycin-resistant enterococcal endophthalmitis following ocular trauma, uniquely caused by Enterococcus gallinarum. The organism demonstrated intrinsic resistance to ceftazidime and vancomycin but responded favorably to a combination of intravitreal and intravenous ampicillin, plus intravitreal amikacin. When faced with a multidrug-resistant organism, the ophthalmologist must consider alternative antibiotic strategies.