may contribute to the pathogenesis of diabetic retinopathy (DR). OBJECTIVES To investigate, in a proof-of-concept clinical trial, whether low-dose oral doxycycline monohydrate can (1) slow the deterioration of, or improve, retinal function or (2) induce regression or slow the progression of DR in patients with severe nonproliferative DR (NPDR) or non-high-risk proliferative (PDR), and to determine the potential usefulness of visual function end points to expedite the feasibility of conducting proof-of-concept clinical trials in patients with DR. DESIGN, SETTING, AND PARTICIPANTS We conducted a randomized, double-masked, 24-month proof-of-concept clinical trial. Thirty patients (from hospital-based retina practices) with 1 or more eyes with severe NPDR or PDR less than Early Treatment Diabetic Retinopathy Study-defined high-risk PDR. INTERVENTIONS Patients were randomized to receive 50 mg of doxycycline monohydrate or placebo daily for 24 months. MAIN OUTCOMES AND MEASURES Change at 24 months compared with baseline in functional factors (frequency doubling perimetry [FDP], Humphrey photopic Swedish Interactive Thresholding Algorithm 24-2 testing, contrast sensitivity, dark adaptation, visual acuity, and quality of life) and anatomic factors (Early Treatment Diabetic Retinopathy Study DR severity level, area of retinal thickening, central macular thickness, macular volume, and retinal vessel diameters). RESULTS From baseline to month 24, mean FDP foveal sensitivity decreased in the placebo group (−1.9 dB) and increased in the doxycycline group (+1.8 dB) (P = .02). A higher mean FDP foveal sensitivity in the doxycycline group compared with the placebo group was detected at 6 months (P = .04), and this significant difference persisted at 12 and 24 months. A difference between the groups was not detected with respect to the other visual function outcomes and all anatomic outcomes assessed. CONCLUSIONS AND RELEVANCE To our knowledge, this is the first observation suggesting a link between a low-dose oral anti-inflammatory agent and subclinical improvement in inner retinal function. Oral doxycycline may be a promising therapeutic strategy targeting the inflammatory component of DR. Furthermore, study results suggest that FDP, which primarily measures inner retinal function, is responsive to intervention and may be a useful clinical trial end point for proof-of-concept studies in patients with DR. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00511875

The finding of a homozygous dominant mutation in a patient with VMD and evidence of widespread retinal degeneration may imply that the pathogenesis of the generalized retinal degeneration differs from that of the macular degeneration. A relative agreement between hyperautofluorescence by FAF, reduced retinal function, and VMD implies that the hyperautofluorescence emanates from lipofuscin and A2E. A potential therapy for VMD, involving the inhibition of the retinoid cycle, is suggested.

After initiation of CSII, the retinal visual pathway of the rods improved with a delay of more than 4 months, over a time scale comparable with the duration of the diabetic retinopathy early worsening response to sustained glycaemia reduction. This indicates that glycaemia has a long-term effect on the disposition of functional capacity in the retinal visual pathway of rod photoreceptors, the cells that appear to be driving the development of diabetic retinopathy.

The change in scotopic signaling amplitude in the outer and middle layers of retina in subjects with diabetes was proportional to the change in capillary glucose. Cone amplitude was not influenced by hyperglycemia in this study.