David M. Kleinman

Infectious Endophthalmitis in Adult Eyes Receiving Boston Type I Keratoprosthesis

PURPOSE To report the clinical characteristics of infectious endophthalmitis after Boston type I keratoprosthesis (K-Pro) implantation. DESIGN Retrospective study. PARTICIPANTS One hundred forty-one adult eyes receiving a K-Pro at a single institution from May 2004 through July 2008. METHODS A retrospective chart review was performed of all adult eyes receiving a K-Pro at the University of Rochester from May 2004 through July 2008. Those patients identified as having been treated for exogenous bacterial endophthalmitis were reviewed for demographic data, indication for K-Pro, bandage contact lens use, prophylactic antibiotic use, timing and clinical presentation of endophthalmitis, gram stain and culture results of intraocular fluid, timing and presentation of any subsequent episodes of endophthalmitis (recurrent endophthalmitis), and preoperative and postoperative visual acuity through August 2010. MAIN OUTCOME MEASURES Incidence of endophthalmitis, time to occurrence, recurrence rates, visual outcomes, and risk factors associated with K-Pro endophthalmitis. RESULTS Ten (7.1%) of 141 eyes of 130 adult patients were diagnosed and treated for bacterial endophthalmitis. Average time to endophthalmitis developing after K-Pro was 9.8 months (standard deviation [SD], 6.2 months; range, 2-25 months). Coagulase-negative staphylococci were identified in 7 eyes. In 7 of the 10 eyes, recurrent endophthalmitis developed that occurred at a mean of 4 months (SD, 3.9 months; range, 1-13 months) after resolution of the initial episode. At each episode of endophthalmitis, no eye was receiving vancomycin ophthalmic drops and most eyes were receiving only fluoroquinolone ophthalmic drops for prophylaxis. CONCLUSIONS Infectious endophthalmitis after K-Pro implantation has a higher incidence, delayed onset, and high risk for recurrence compared with postoperative endophthalmitis associated with more common intraocular procedures such as cataract surgery. The concurrent use of topical vancomycin is recommended because it seems to be important in reducing the incidence and recurrence of endophthalmitis and because fluoroquinolone ophthalmic drops do not seem to be sufficient prophylaxis in these eyes.

A randomized, dose-escalation study of subconjunctival and intravitreal injections of sirolimus in patients with diabetic macular edema.

OBJECTIVE To evaluate the safety and tolerability of a single subconjunctival (SCJ) or intravitreal (IVT) injection of an ophthalmic sirolimus formulation in eyes with diabetic macular edema (DME). DESIGN Randomized, open-label, dose-escalating phase I study. PARTICIPANTS Fifty eyes among 50 patients with DME, retinal thickness ≥ 300 microns and best-corrected visual acuity (BCVA) 20/40 to 20/200. METHODS A single dose of sirolimus administered SCJ (220, 440, 880, 1320, or 1760 μg) or IVT (44, 110, 176, 264, or 352 μg) on day 0; observation through day 90. MAIN OUTCOME MEASURES Primary end points were the frequency and severity of ocular and systemic adverse events. Secondary end points were changes in BCVA and retinal thickness. RESULTS No dose-limiting toxicities were observed and ocular adverse events were mostly mild and transient. Conjunctival hyperemia, hemorrhage, and edema were common after the SCJ injection procedure and conjunctival hemorrhage was common after the IVT injection procedure. Three patients experienced ocular adverse events considered possibly related to study drug: Conjunctival edema and reduced visual acuity were reported in 1 SCJ patient each and iritis was reported in 1 IVT patient. No serious ocular adverse events were reported. No nonocular adverse events were considered related to study drug. Systemic exposure to sirolimus was low, with blood concentrations below levels necessary for systemic immunosuppression. For the SCJ group (n = 25), a median increase in BCVA started at day 7 (5.0 letters) and was 3.0, 4.0, and 4.0 letters at days 14, 45 and 90, respectively. At day 45, median decrease in retinal thickness was -23.7 μm. For the IVT group (n = 25), the median increase in BCVA was 2.0 letters at day 7; at days 14, 45, and 90, the median increase was maintained (4.0 letters); the median decrease in retinal thickness was -52.0 μm at day 45. CONCLUSIONS Locally administered sirolimus was well-tolerated with minimal systemic exposure at all doses tested in this small phase I population. These findings support advancing the present sirolimus formulation into phase II studies. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

RAPAMYCIN INHIBITS VEGF-INDUCED MICROVASCULAR HYPERPERMEABILITY IN VIVO

Microcirculation (2010) 17, 1–9. doi: 10.1111/j.1549‐8719.2009.00012.x

Retinopathy in sickle cell trait: Does it exist?+

BACKGROUND Patients with sickle cell trait and concomitant systemic disease are known to be at risk for proliferative retinopathy. However, there are reports of retinopathy in patients with sickle cell trait without systemic disease. There are no population-based studies addressing the risk of sickle cell retinopathy in this group. We performed a study to clarify the relation between sickle cell trait and retinopathy in healthy subjects. METHODS We reviewed the medical records of 100 children with sickle cell disease who attended the Sickle Cell Clinic at the Hospital for Sick Children, Toronto. We then contacted 200 parents with sickle cell trait, of whom 32 agreed to participate in the study. All participants were proven to have hemoglobin AS status with prior hemoglobin electrophoresis. An ophthalmologic history was obtained, and a complete ophthalmologic examination was performed. We defined sickle cell retinopathy as any salmon patch hemorrhages, iridescent spots, black sunbursts, retinal neovascularization or retinal detachment. The evaluation also included attempts to identify the more subtle signs of sickle cell retinopathy, such as optic nerve head vascular changes, vascular tortuosity, macular changes (e.g., microaneurysms and vascular loops) and peripheral arteriovenous anastamoses. Blood samples were obtained for complete blood count, reticulocyte count and smear. RESULTS We found no cases of sickle cell retinopathy among the 32 subjects. Ten of 30 subjects had a high reticulocyte count (greater than 120 x 10(9)/L); however, there were no associated eye findings in this subgroup. INTERPRETATION Our results indicate that there is no increased risk of retinopathy in healthy people with sickle cell trait.

A systematic review and meta-analysis to compare the efficacy of acyclovir 3% ophthalmic ointment to idoxuridine in curing herpetic keratitis by Day 7 of treatment

BackgroundThis objective of the review and analysis is to demonstrate that acyclovir (ACV) 3% ophthalmic ointment is superior to idoxuridine (IDU) in treating herpetic keratitis (HK) presenting as dendritic and geographic ulcer sub-types.MethodsData sources: Publications in human subjects were identified by searching the Ovid MEDLINE database through April 2011, combining medical subject headings (MESH) “Keratitis, Herpetic/” AND “Acyclovir/” limiting by the key words “topical” OR “ointment” and also restricted to MESH “Administration, Topical/” OR “Ointments/”. The results were cross checked with the references used in the Cochrane Database Syst Rev. 1:1–134, 2009 and GlaxoSmithKline clinical documents related to acyclovir.Study selection: Randomized, double-masked studies in subjects diagnosed with HK with head to head comparator arms of ACV ophthalmic ointment and topical IDU that had actual or calculable healing rates at Day seven.Data extraction: Data independently extracted from identified articles by two authors of this manuscript.Data synthesis: Data from seven randomized, controlled trials (RCT) evaluating 432 subjects that met inclusion criteria (214 were treated with ACV and 218 were treated with IDU) and had Day seven healing rates calculable. All sub-classified lesions were identified as either dendritic ulcers (n = 185) or geographic ulcers (n = 35). The Cochran-Mantel-Haenszel (CMH) method in Biometrics 10:417-51, 1954 and JNCI 22:719-48, 1959, controlling for study, was performed as the primary analysis using SAS v9.Homogeneity was assessed using Breslow-Day-Tarone (BDT) test in IARC 1:1-32, 1980 and Biometrika 72:91-5, 1985. The analysis was performed with outliers removed to assess their impact.ResultsACV showed statistically significant greater odds of healing HK at Day seven in all subjects (Odds Ratio 3.95, 95% CI2.60, 6.00, p <0.0001), in dendritic ulcers (Odds Ratio 4.22, 95% CI: 2.14, 8.32; p < 0.0001) and geographic ulcers (Odds Ratio 5.31, 95% CI: 1.09, 25.93; p =0.0244).ConclusionACV 3% ophthalmic ointment is a valuable intervention for dendritic and geographic corneal ulcers. ACV and IDU were generally well tolerated in the studies reviewed.

A compact fundus camera to improve global access to retinal and optic nerve imaging

To reduce rates of blindness and vision loss from treatable eye conditions, improving patient access to early diagnosis is critical. Identification and treatment of eye disease are vital to preserve the function of the retina and optic nerve, as current therapies can delay or avoid the onset of blindness. To conduct eye examinations, clinicians routinely use the widely available direct ophthalmoscope, which illuminates the eye’s interior for examination, but the instrument has limited utility. It has a small field of view, provides a fleeting image, and leaves no examination record. Ophthalmologists and optometrists utilize more advanced and accurate examination techniques, but access to these types of providers is far from universal. Traditional fundus cameras, which photograph the eye’s interior to monitor disease, are a valuable alternative technology, but they are expensive, bulky, and typically used by trained technicians in well-funded eye care centers. As a result, a lack of a quality routine retinal examination puts many people at risk for vision loss. Several handheld fundus cameras have emerged in the marketplace, including Volk Pictor, Nidek NM-200D, OptoMed Smartscope, and Kowa Genesis. The use of these cameras is hampered by their precise alignment requirements: the task of aiming such a camera into a patient’s pupil at the correct angle is challenging for the technician holding the camera. Furthermore, the camera focusing mechanism needs constant adjustment to match the patient’s changing accommodation, which can confuse the camera’s autofocusing algorithms. These constraints require that the operator continually visualizes the retinal image provided by the camera, leading to a need for larger systems that have fewer practical applications. Our approach solves these problems and offers opportunities to miniaturize the technology. Steven Feldon and Geunyoung Figure 1. Conceptual rendering of the fundus camera, which is held in contact with the cornea. (Image courtesy of KEK Associates, Inc.)