dorzolamide and Macular-Degeneration

X-linked retinoschisis is the leading cause of macular degeneration in males and leads to splitting within the inner retinal layers leading to visual deterioration. Many missense and protein truncating mutations have now been identified in the causative retinoschisis gene (RS1) which encodes a 224 amino acid secretory retinal protein, retinoschisin. Retinoschisin octamerisation is implicated in cell-cell interactions and cell adhesion perhaps by interacting with beta2 laminin. Mutations cause loss of retinoschisin function by one of the three mechanisms: by interfering with protein secretion, by preventing its octamerisation or by reducing function in the secreted octamerised protein. The development of retinoschisis mouse models have provided a model system that closely resembles the human disease. Recent reports of RS1 gene transfer to these models and the sustained restoration of some retinal function and morphology suggest gene replacement may be a possible future therapy for patients.

Topics: Adult; Age of Onset; Animals; Biopolymers; Cell Adhesion; Child; Child, Preschool; Chromosomes, Human, X; Diagnosis, Differential; Diagnostic Techniques, Ophthalmological; Disease Models, Animal; Disease Progression; Eye Proteins; Female; Genes, X-Linked; Genetic Carrier Screening; Genetic Counseling; Genetic Therapy; Humans; Infant; Macular Degeneration; Male; Mice; Phenotype; Prevalence; Protein Structure, Tertiary; Retinoschisis; Sulfonamides; Thiophenes

Numerous studies have confirmed the enhancement of ocular circulation by carbonic anhydrase inhibitors (CAIs). Topical CAI treatment with dorzolamide averts the significant pericentral visual function loss accompanying retinal and choroidal vasoconstriction during acute hyperventilation-induced hypocapnia. This study was designed to discern whether dorzolamide might similarly enhance macular function in patients with age-related maculopathy (ARM).. In a masked, placebo-controlled study, 40 patients with ARM and acuity > 20/50 were randomized to receive either dorzolamide or placebo for 12 weeks, thrice daily. After pre-study perimetric training, pericentral function (mean sensitivity) was quantified using Humphrey 10-2 short-wavelength automated perimetry (SWAP), before and after 12 weeks of topical therapy.. Dorzolamide-treated eyes demonstrated a significant increase in mean sensitivity of + 1.55 dB (p = 0.04); placebo-treated eyes showed no significant change (+ 0.58 dB; p = 0.10). Given the non-significant increase of mean sensitivity in the placebo-treated group, fewer than 100 subjects per group would be required to afford > 70% power to yield a significant direct comparative difference between treatment and placebo in a prospective, randomized study of equally short duration.. This study demonstrated a significant increase in short-wavelength sensitivity in ARM with dorzolamide and the lack thereof with placebo. These encouraging pilot study data suggest a potential role for topical CAIs in ARM patients, and establish objective parameters for prospective studies to further evaluate the effects of dorzolamide in ARM.

Topics: Administration, Topical; Aged; Carbonic Anhydrase Inhibitors; Double-Blind Method; Female; Humans; Macular Degeneration; Male; Pilot Projects; Prospective Studies; Sulfonamides; Thiophenes; Visual Acuity; Visual Field Tests; Visual Fields

To comprehensively evaluate the effects of dorzolamide on the choroidal and retinal circulation in patients with age related macular degeneration (AMD).. In this randomised, double masked, parallel study, 36 non-exudative AMD patients were randomised in a 2 to 1 fashion to placebo versus topical dorzolamide and underwent assessment of their choroidal and retinal circulation. Scanning laser ophthalmoscope indocyanine green angiograms (ICGA) were analysed by a new area dilution analysis technique. Four areas in the perifoveal region and two areas in the temporal peripapillary region were evaluated by plotting intensity of fluorescence of each area over time. The means of the choroidal filling times and the heterogeneity of the filling times were assessed. Scanning laser ophthalmoscope fluorescein angiography (FA) was evaluated for retinal arteriovenous passage (AVP) times by plotting intensity of fluorescence of retinal vessels over time. Assessment was performed at baseline and at 4 months.. Compared to placebo, AMD patients treated with dorzolamide showed a significantly increased rapidity of choroidal filling in the superior and inferior peripapillary regions (p=0.007, p=0.02, respectively). No significant difference in choroidal filling times was found in any of the perifoveal areas (p=0.9). Also, on FA assessment, treatment with dorzolamide showed no statistical differences in AVP times (p=0.19).. Dorzolamide may increase peripapillary choroidal perfusion in non-exudative AMD patients. Further studies are merited.

Topics: Aged; Antihypertensive Agents; Choroid; Coloring Agents; Double-Blind Method; Female; Fluorescein Angiography; Humans; Indocyanine Green; Macular Degeneration; Male; Middle Aged; Retinal Vessels; Sulfonamides; Thiophenes

Topics: Humans; Macular Degeneration; Sulfonamides; Thiophenes; Timolol