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We investigated risks and hazard rates of developing chronic ocular graft-versus-host disease (oGVHD) in a large nationwide, single centre study by using the criteria proposed by “The International Chronic oGVHD Consensus Group”. This retrospective study included 1407 consecutive adults who underwent allogeneic haematopoietic stem cell transplantation (HSCT). Patients were examined by an ophthalmologist according to the hospital’s guidelines: baseline examination before HSCT, annually up to 5 years after HSCT. The 186 (13%) had dry eye disease before HSCT. The 5-year cumulative incidence of oGVHD was 18% (95% CI: 15–21) after myeloablative (MA) and 35% (95% CI: 30–39) after non-myeloablative conditioning (NMA). Factors associated with the rate of oGVHD were assessed separately according to conditioning regimen by using multiple Cox regression analyses. Factors that increased the rate in the MA group: Malignant disease, Schirmer’s test≤10 mm/5 min before transplantation, use of female donor, matched unrelated donor, peripheral blood as stem cell source, and grade III-IV acute GVHD. Factors that increased the rate in the NMA group: Schirmer’s test≤10 mm/5 min before transplantation and higher recipient age. We recommend a baseline ophthalmological examination before HSCT since many of the patients have signs of dry eyes before transplantation which increased the risk and rate of developing oGVHD.

To compare the risk of surgical complications after primary surgical intervention for postoperative endophthalmitis after cataract surgery (PE) in cases that underwent a pars plana vitrectomy (PPV) or a vitreous tap (VT) in Denmark in the calendar period 1 January 2000 to 30 June 2011. Retrospective, register- and chart-based study. A total of 121 PE cases were identified and followed up to 12.8 years. The overall risk of surgical complications in PE cases that underwent a PPV and a VT was 24.2 and 36.7 %, respectively. This difference was non-statistically significant (p = 0.18). In all, 9.9 % of the PE cases had more than one surgical complication, and 97 % of the primary surgical complications occurred within the first 5 months. There was no statistically significant difference in the risk of retinal detachment (p = 0.45), surgery for PE (p = 0.22), intraocular lens removal (p = 0.19), or removal of the eye (p = 0.69) between the two groups. PE cases that underwent a VT had a statistically significantly higher risk of surgery for vitreous opacities (p = 0.047) compared to a PPV. In all, 27.3 % of all cases developed a surgical complication after primary surgical intervention for PE. If a PE case did not have a surgical complication within the first 5 months, it was highly unlikely that a new surgical complication would occur. A VT was not associated with a statistically significantly higher overall risk of surgical complications compared to a PPV.

The functional consequence of long-term retinal detachment in the porcine model is examined by multifocal electroretinography (mfERG). Retinal detachment (RD) in humans leaves permanent visual impairment, despite anatomical successful reattachment surgery. To improve treatment, adjuvant pharmaceutical therapy is needed, and can only be tested in a suitable animal model. The porcine model is promising and the mfERG is well validated in this model. RD was induced in 18 pigs by vitrectomy and healon injection of various concentrations. Preoperatively and 6 weeks postoperatively eight animals were examined by mfERG. The major component P1 was analyzed statistically. Indirect ophthalmoscopy and bilateral color fundus photography (FP) were performed. Selected animals underwent high-resolution optical coherence tomography (OCT). Examination by ophthalmoscopy and FP showed that the RDs remained detached for the 6 weeks of follow-up. The P1 amplitude of the mfERG did not differ significantly between the detached areas, the surrounding attached areas, and the healthy eye (p = 0.25). Similarly, P1 implicit time did not differ between the areas (p = 0.85). The lack of functional consequences of long-term RD makes the porcine model unsuitable for examining adjuvant pharmaceutical RD treatment. Future studies should focus on foveated primates.

Carbonic anhydrase inhibitors (CAIs) increase blood flow in the brain and probably also in the optic nerve and retina. Additionally they elevate the oxygen tension in the optic nerve in the pig. We propose that they also raise the oxygen tension in the retina. We studied the oxygen tension in the pig retina and optic nerve before and after dorzolamide injection. Also the retinal vessel diameters during carbonic anhydrase inhibition were studied.A polarographic oxygen electrode was placed transvitreally immediately over the retina or the optic disc in anaesthetised pigs. The oxygen tension was recorded continually and 500 mg dorzolamide was injected intravenously. Retinal vessel diameters were analysed from monochromatic fundus photographs taken before and after injection of dorzolamide.Baseline retinal oxygen tension (RPO2) was 3.34+/-0.50 kPa (mean +/- SD, n=6) and baseline optic nerve oxygen tension (ONPO2) was 3.63+/-1.00 kPa. RPO2 was increased by 0.36+/-0.11 kPa (n=6, P=0.025) and ONPO2 by 0.73+/-0.34 kPa (n=6, P=0.003) 30 min after dorzolamide administration. The retinal arterioles was significantly dilated by 13+/-7% (n=5, P=0.016) and the retinal venules by 12+/-8% (n=5, P=0.030) 30 min after injection of dorzolamide.Retinal and optic nerve oxygen tension increased with systemic administration of dorzolamide. The retinal vessels dilated, probably causing increased blood flow inducing the observed increase in RPO2. The increased oxygenation of retina by CAI may offer therapeutic possibilities in ischaemic diseases of the retina and optic nerve.

Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian individuals than in pigmented races. In predominantly Caucasian populations, the age-standardised prevalence of AMD in at least one eye is 7760 cases per million. The age-standardised cumulated 1-year incidence of AMD in at least one eye is 1051 cases per million individuals. AMD is the most important single cause of blindness among Caucasian individuals in developed countries. Blindness resulting from AMD rarely occurs before age 70, and most cases occur after age 80. The age-standardised 1-year incidence of legal blindness resulting from AMD is 212 cases per million. Two-thirds of AMD cases have CNV (exudative cases); the remainder has only geographic atrophy. In cross-sectional population-based studies about 45% of eyes with AMD have visual acuity reduced to 20/200 or worse. This is true both for exudative AMD and pure geographic atrophy. Age and genetic predisposition are known risk factors for AMD. Smoking is probably also a risk factor. Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires a fluorescein angiographic study and a physician capable of interpreting it. For CNV not involving the foveal centre, the only evidence-based treatment is laser photocoagulation. For AMD cases with subfoveal CNV, good visual acuity, and predominantly classic fluorescence pattern on fluorescein angiography, photodynamic therapy with verteporfin is the treatment of choice. Photodynamic therapy is also effective in eyes with pure occult CNV and evidence of recent disease progression. For new subfoveal CNV with poor vision and recurrent CNV, laser photocoagulation can be considered.

At high concentrations, certain fluorophores undergo self-quenching, i.e., fluorescence intensity decreases with increasing fluorophore concentration. Accordingly, the self-quenching properties can be used for measuring water volume changes in lipid vesicles. In cells, quantitative determination of water transport using fluorescence self-quenching has been complicated by the requirement of relatively high (mM) and often toxic loading concentrations. Here we report a simple method that uses low (μM) loading concentrations of calcein-acetoxymethyl ester (calcein-AM) to obtain intracellular concentrations of the fluorophore calcein suitable for measurement of changes in cell water volume by self-quenching. The relationship between calcein fluorescence intensity, when excited at 490 nm (its excitation maximum), and calcein concentration was investigated in vitro and in various cultured cell types. The relationship was bell-shaped, with the negative slope in the concentration range where the fluorophore undergoes fluorescence self-quenching. In cultured retinal pigment epithelial cells, calcein fluorescence and extracellular osmolarity were linearly related. A 25-mOsm hypertonic challenge corresponded to a decrease in calcein fluorescence with high signal-to-noise ratio (>15). Similar results were obtained with the fluorophore BCECF when excited at its isosbestic wavelength (436 nm). The present results demonstrate the usefulness of fluorescence self-quenching to measure rapid changes in cell water volume.