Phase 1 Study of THR-687, a Novel, Highly Potent Integrin Antagonist for the Treatment of Diabetic Macular Edema.

Purpose: To evaluate the safety and preliminary efficacy of THR-687 in patients with center-involved diabetic macular edema (DME). Design: Phase 1, open-label, multicenter, 3 + 3 dose-escalation study with 3-month follow-up. Participants: Patients 18 years of age or older with visual impairment resulting from DME. Methods: Single intravitreal injection of THR-687 (0.4 mg, 1.0 mg, or 2.5 mg). Main Outcome Measures: The primary outcome measure was the incidence of dose-limiting toxicities (DLTs). The secondary outcome measure was the incidence of adverse events (AEs), including the occurrence of laboratory abnormalities. Exploratory outcome measures included changes from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST), assessments of ischemia and leakage on fluorescein angiography, and THR-687 levels in plasma. Results: Twelve patients were treated: 3 patients received 0.4 mg of THR-687, 3 patients received 1.0 mg of THR-687, and 6 patients received 2.5 mg of THR-687. Most patients were men (9/12 patients). Their mean age was 57.8 years. No DLTs or serious AEs were reported at any of the dose levels tested. Overall, 9 AEs in the study eye were reported for 5 of 12 patients. Of those, 4 AEs in 3 of 12 patients were deemed treatment related by the investigator, all of which were mild, started on the day of the injection, and had resolved within 28 days without treatment. Overall, mean gains from baseline in BCVA were observed at all study visits with a rapid onset (7.2 Early Treatment Diabetic Retinopathy Study [ETDRS] letters at day 7) and a durability up to the end of the study (8.3 ETDRS letters at month 3). A mean decrease in CST was observed up to month 1. Overall, the mean BCVA gains and CST decreases were highest at the highest THR-687 dose level tested. THR-687 was undetectable in plasma at 7 days after the injection. Conclusions: At all dose levels tested, a single intravitreal injection of THR-687 was safe and well tolerated. Preliminary efficacy was observed by a rapid gain in BCVA with 3 months' durability and a decrease in CST up to 1 month after the injection.

Intravitreal Bevacizumab for Macular Edema from Idiopathic Retinal Vasculitis, Aneurysms, and Neuroretinitis.

To assess the potential visual benefit of intravitreal bevacizumab in a patient with macular edema from idiopathic retinal vasculitis, aneurysms, and neuroretinitis, an intravitreal injection of bevacizumab (1.25 mg) was given. Within 1 week, visual acuity improved from 20/60 to 20/30 and optical coherence tomography demonstrated resolution of macular edema. There was no adverse effect. The macular edema returned after 3 months, and a repeat treatment of bevacizumab led to resolution of macular edema once again. An intravitreal injection of bevacizumab may provide potential short-term visual benefit in patients with macular edema from idiopathic retinal vasculitis, aneurysms, and neuroretinitis.

Physician assessment of changing lesion size of predominantly classic choroidal neovascular membranes in age-related macular degeneration.

BACKGROUND AND OBJECTIVE: To quantify the interpretation of fluorescein angiograms of evolving predominantly classic choroidal neovascularization in age-related macular degeneration. PATIENTS AND METHODS: Thirty-six fluorescein angiograms of predominantly classic choroidal neovascularization were used to define 22 fluorescein angiogram pairs. Imaging software was used to measure surface area and greatest linear dimension (GLD). Six retina physicians estimated the change in surface area and GLD for each pair before and after demarcation of the lesions' borders and GLD. RESULTS: For enlarging lesions, the smallest changes consistently detected by physicians were a 5% to 15% increase in surface area and a 5% to 15% increase in GLD; for shrinking lesions, they were a 5% to 15% decrease in surface area and a 5% to 15% decrease in GLD. Linear regression demonstrated moderate correlation between physician and software estimates of surface area and GLD change (r(2) = 0.50 and 0.67, respectively; P < .001), which was higher with lesion demarcation (r(2) = 0.91 and 0.93, respectively; P < .001). CONCLUSION: Computer-assisted demarcation of lesion surface area and GLD reduced variability in physicians' estimates of choroidal neovascularization size change and improved correlation with software measurements.

Intravitreal bevacizumab for macular edema from idiopathic juxtafoveal retinal telangiectasis.

To assess the potential visual benefit of intravitreal bevacizumab in a patient with idiopathic juxtafoveal retinal telangiectasis refractory to focal laser treatment, an intravitreal injection of bevacizumab (1.25 mg) was given. Within 1 week, visual acuity improved from 20/50 to 20/25 and optical coherence tomography demonstrated complete resolution of macular edema. There was no adverse effect. The macular edema recurred after 3 months, requiring a repeat injection of bevacizumab with subsequent resolution of macular edema. An intravitreal injection of bevacizumab may provide potential short-term visual benefit in patients with macular edema from idiopathic juxtafoveal retinal telangiectasis.

Retinal complications of bone marrow and solid organ transplantation.

PURPOSE OF REVIEW: A review is presented of the current literature on retinal complications of bone marrow and solid organ transplantation. RECENT FINDINGS: Retinal complications of bone marrow and solid organ transplantation include microvascular retinopathy, infection, and hemorrhagic findings. Other clinical observations include central serous chorioretinopathy, bilateral optic disc edema, and cyclosporine-related retinal toxicity. The cause of these clinical findings is likely to be multifactorial, resulting from the combined effects of cyclosporine, total body irradiation, infections, high-dose chemotherapy, and recurrent malignancies. SUMMARY: Understanding of these clinical entities of the posterior segment is important in minimizing the potentially sight-threatening complications from bone marrow and solid organ transplantation.

Lensectomy and vitrectomy decrease the rate of photoreceptor loss in rhodopsin P347L transgenic pigs.

BACKGROUND: Photoreceptor degeneration in retinitis pigmentosa (RP) runs an inevitable, gradually progressive course. A wide variety of growth factors of different origins have been shown to slow the rate of degeneration in some rodent models of RP. Recently, lens-derived neurotrophic factors have been shown to rescue degenerating ganglion cells in crush models of the optic nerve. Our objective was to evaluate the potential rescue effect of lensectomy and vitrectomy (L&V) on photoreceptor degeneration in a large-animal model, the rhodopsin P347L transgenic pig. METHODS: We operated on one eye of each of 49 3-week-old pigs--15 vitrectomies and 34 L&V, 6 of which received steroids. Retinal paraffin sections were prepared for all eyes, in addition to immunohistochemistry in four eyes, 8 weeks after L&V. RESULTS: At eight weeks after L&V, operated eyes showed significantly more nuclei in the outer nuclear layer (ONL) than the unoperated fellow eyes. The better preservation of the ONL persisted but was less prominent by 20 weeks after surgery. Steroid treatment did not markedly reduce the better preservation of the ONL seen at 8, 10, and 12 weeks after surgery. The significant difference in cell count between operated and unoperated eyes in the L&V group at 8 weeks was due to the difference in the number of rods, not the cones. CONCLUSION: Lensectomy and vitrectomy delay photoreceptor degeneration in rhodopsin P347L transgenic pigs. Lens-related rescue effect is a probable reason for the delayed degeneration.

Microsporidial keratoconjunctivitis in a healthy patient with a history of LASIK surgery.

PURPOSE: To describe a case of microsporidia corneal infection in a HIV-negative patient who did not wear contact lenses. METHOD: Case report and review of literature. RESULTS: This is the first case report of a human immunodeficiency virus-negative individual, a non-contact lens wearer, with microsporidia infection. CONCLUSION: Microsporidia keratoconjunctivitis may occur in healthy subjects with no antecedent contact lens wear.