Endothelin-1 Plasma Levels in Patients with both Retinitis Pigmentosa and Flammer Syndrome.

BACKGROUND: Endothelin-1 is a strong endogenous vasoconstrictor and is also an agent reducing the ocular blood flow. Patients with retinitis pigmentosa are known to have reduced ocular blood flow. This can be secondary to retinal atrophy, but may also partially result from an additional condition, such as a Flammer syndrome. The aim of the study was to investigate whether the endothelin-1 plasma levels in retinitis pigmentosa patients with and without Flammer syndrome are different. PATIENTS AND METHODS: In the study we included patients with clinical signs and symptoms of retinitis pigmentosa, confirmed by electrophysiological findings. Blood samples were obtained from 6 retinitis pigmentosa patients with and 4 without Flammer syndrome. The results were related to 30 age- and sex-matched control subjects. Endothelin-1 plasma levels were determined by specific radioimmunoassay. RESULTS: The endothelin-1 plasma levels in retinitis pigmentosa patients with Flammer syndrome were significantly higher than those without Flammer syndrome. The mean (±SD) endothelin-1 levels (pg/mL) in retinitis pigmentosa patients with Flammer syndrome were 4.95 (±1.74), range: (2.37-6.76), whereas in patients without Flammer syndrome they were 1.10 (±0.08), range: 1.00-1.20. Our own normal values are: 1.56 (±0.30), range: (0.90-2.13). All retinitis pigmentosa patients with increased endothelin-1 plasma levels had signs and symptoms related to a Flammer syndrome, such as cold extremities, low blood pressure, reduced feeling of thirst, increased sensitivity in general, e.g., increased sensitivity to certain drugs, increased pain sensitivity and increased sense of smell. CONCLUSION: Endothelin-1 plasma levels were increased in retinitis pigmentosa patients with but not in patients without Flammer syndrome. Many questions remain open: Why so many retinitis pigmentosa patients suffer from Flammer syndrome, why is the endothelin-1 level in such patients higher than in healthy subjects with Flammer syndrome, how much of the ocular blood flow reduction is due to retinal degeneration and how much to the Flammer syndrome? We hypothesise that Flammer syndrome leads to an additional increase of the endothelin-1 level and an additional decrease of ocular blood flow in retinitis pigmentosa patients. Further studies are needed to analyse the causal relationship between retinitis pigmentosa and Flammer syndrome and evaluate potential therapeutic implications.

The effect of ranibizumab versus photodynamic therapy on DNA damage in patients with exudative macular degeneration.

PURPOSE: To compare the effect of ranibizumab treatment versus photodynamic therapy (PDT) on single-stranded DNA damage in circulating leukocytes in patients with exudative age-related macular degeneration (AMD). METHODS: A comparative quantification of single-stranded DNA breaks was performed in circulating leukocytes of AMD patients before and 30 min, 45 min, 60 min, and 24 h after two different modes of therapy: a) PDT; and b) intravitreal ranibizumab injection. DNA breaks lead to smaller pieces of DNA, which in an electrical field, migrate out of the nucleus forming a tail. Damage of an individual cell was quantified as a comet tail moment. The proportion of non-zero values compared to the total number of observations was referred to as "amount of DNA damage" expressed in arbitrary units (AU). Comparisons between time points and study groups were assessed using a linear mixed-effect model. RESULTS: PDT induced an increase in the amount of single-stranded DNA damage in the circulating leukocytes from 0.2 AU (before treatment) to 0.53 AU (30 min after treatment). This increase was significant (p=0.004). In contrast, after ranibizumab treatment, the DNA damage in the circulating leukocytes remained unchanged. CONCLUSIONS: PDT purposely induces a local oxidative stress to damage the newly formed vessels. Our results indicate an additional systemic oxidative stress, apparent as amount of single-stranded DNA damage in the circulating leukocytes, for at least 30 min after treatment.

Macula-off retinal detachment--a matter of time?

BACKGROUND: The aim of this study was to determine the influence of the lag time between macular detachment and surgical intervention on post-operative visual acuity gain in patients with rhegmatogenous macula-off retinal detachment. PATIENTS AND METHODS: We retrospectively evaluated the medical records of 62 consecutive patients having undergone scleral buckling surgery for rhegmatogenous macula-off retinal detachment. The correlation of gender, age, refraction, number of retinal breaks, development of cataract during follow-up, pre-operative visual acuity and timing of surgical intervention with final visual acuity and post-operative visual acuity gain were determined. Mean follow-up time was 12.7 months. RESULTS: A correlation with final visual acuity was found for pre-operative visual acuity and lag between the beginning of symptoms and surgical intervention. A correlation with visual acuity gain was found only for timing of surgical procedure. When divided into subgroups operated after 0, 1-3, 4-6, or 7-9 days, respectively, visual recovery was better the earlier the patients underwent surgical repair. Compared to surgery at day 0, statistical significance was found only for patients operated 4 or more days after the occurrence of symptoms. CONCLUSION: The first three days seem to represent a relatively safe period during which surgery for macula-off retinal detachment may be postponed without compromising the patient's visual prognosis.

Eye disorders in diabetes: potential drug targets.

Diabetes Mellitus (DM) is a serious medical problem that causes long-term systemic complications and considerable associated morbidity. DM can cause retinopathy (DRP), maculopathy, cataract, optic neuropathy, defects of eye muscles. DM is a risk factor for acute infectious conjunctivitis, bacterial keratitis, herpes virus infections and endophtalmitis. Elevated blood glucose induces structural, physiological and hormonal changes which affect retinal capillaries. DRP is recognized by loss of pericyte function and capillary occlusions together leading to breakdown of blood-retinal barrier, edematous changes and proliferation of vessels and fibrous tissue. Depending on stage of DRP, there are different preferable therapeutic approaches applied. In the case of ETDRS, in the area of leakage focal treatment should be performed, while panretinal photocoagulation is applied towards ischemic areas or beginning proliferations. Vitreal haemorrhage followed by fibroproliferative changes or tractional retinal detachment is treated by vitrectomy alone or in combination with ILM peeling. In pathogenesis of DRP, Insulin Growth Factor (IGF-1) can play an important role in production of VEGF (Vascular Endothelial Growth Factor). Hypoxia can up-regulate VEGF expression levels leading to pathologic ocular neovascularisation. An application of intravitreal corticosteroid treatment modulates vascular permeability by suppressing the production of VEGF, reducing both extracellular matrix metalloproteinase activity and basic fibroblast growth factor, decreasing major histocompatibility complex 2 Ag expression levels, and inhibiting activity of inflammatory cells. Clinical effects of treatment using intravitreal corticosteroids are evaluated by reduction of macular thickness and visual improvement. Intravitreal use of Anti-VEGF drugs, Pegaptanib, Ranibizumab and Bevacizumab can modify vasoproliferation, trigger macular edema, and, therefore, influence a prognosis for visual loss.