Eyelid Disorders in Ophthalmology Practice: Results from a Large International Epidemiological Study in Eleven Countries.

PURPOSE: Anecdotal evidence suggests that eyelid disorders are common, although estimates of prevalence vary. The current study determines the prevalence of eyelid disorders, meibomian gland dysfunction (MGD) and related diseases (specifically ocular surface disease) in a population of patients presenting for routine ophthalmologic consultations. METHODS: This cross-sectional epidemiologic survey evaluated patients presenting for routine ophthalmic visits. During the consultation an ophthalmologist completed a questionnaire, and each patient underwent an ophthalmic examination and completed a quality of life questionnaire. RESULTS: Three hundred forty-nine ophthalmologists, recruited from 11 countries, provided data on 6525 patients. Patients were predominantly females (61.6%). The mean age of the study population was 57.0 ± 17.6 years. Eyelid disorders were diagnosed in 5109 (78.3%) patients and were statistically associated with: atopic dermatitis, seborrheic dermatitis, dry eye, age-related macular degeneration, diabetes, cataract, allergy and MGD (P < 0.05, all associations). Eyelid abnormalities were identified in 59.6% of patients; conjunctival or corneal abnormalities were observed in 64.9% and 28.1% of patients, respectively. MGD was diagnosed in 54.3% patients and was statistically significantly associated with the presence of eyelid disorders and eyelid margin abnormalities (P < 0.001, both comparisons). Dry eye was diagnosed in 61.8% of patients. Concurrent dry eye and MGD were present in 67.6% of patients. Most patients reported some degree of impaired vision and daily/work activities related to dry eye. Impact on contact lens usage, emotions and quality of sleep was also reported. The effects on daily life were associated with the presence of MGD. CONCLUSION: In conclusion, eyelid disorders were highly prevalent in this 'real-world' population of patients from ophthalmology clinics. Routine ophthalmologic consultations provide an opportunity to improve patient quality of life and to modify topical therapy in patients who may be predisposed to eyelid disorders.

Dorzolamide increases retinal oxygen tension after branch retinal vein occlusion.

PURPOSE: To study the effect of dorzolamide on the preretinal oxygen tension (RPO(2)) in retinal areas affected by experimental branch retinal vein occlusion (BRVO) in pigs. METHODS: Experimental BRVO was induced by diathermy close to the optic disc. RPO(2) was measured with an oxygen-sensitive electrode 0.5 mm above the BRVO-affected area, which was compared to the retinal areas not affected by BRVO. In one group of five pigs, RPO(2) was measured at baseline, 1 and 3 hours after BRVO, and after intravenous injection of 500 mg dorzolamide. In a second group of five pigs, RPO(2) was measured 1 week after the BRVO, both before and after intravenous injection of 500 mg dorzolamide. RESULTS: The average baseline RPO(2) was 2.64 +/- 0.09 kPa (mean +/- SD). In the BRVO-affected areas, RPO(2) decreased significantly (by 0.67 +/- 0.29 and 0.94 +/- 0.13 kPa) at 1 hour and 3 hours after BRVO induction. In the non-BRVO areas RPO(2) increased significantly (by 0.51 +/- 0.14 kPa) 1 hour after BRVO induction, but subsequently decreased and reached baseline 3 hours after BRVO induction. One week after BRVO induction, RPO(2) was 0.67 +/- 0.29 kPa lower in affected areas when compared with the non-BRVO areas. In the BRVO-affected areas, dorzolamide increased RPO(2) significantly (by 0.36 +/- 0.21 kPa at 3 to 4 hours and by 0.67 +/- 0.40 kPa) 1 week after BRVO induction. CONCLUSIONS: Retinal hypoxia induced by experimental BRVO remained significant 1 week after BRVO. Dorzolamide increased retinal oxygen tension in the BRVO-affected areas both at 4 hours and 1 week after experimental BRVO in pigs.

Ultrasonic mirror image from ruthenium plaque facilitates calculation of uveal melanoma treatment dose.

BACKGROUND/AIMS: To present a new method to determine dose depth and the distance from the concave side of the plaque to the tumour base in patients with uveal melanoma treated with ruthenium-106 based on ultrasonic mirror image. METHODS: We used the mirror image associated with ultrasound during plaque brachytherapy to determine intraobserver reproducibility and interobserver agreement between two surgeons. 230 eyes with primary uveal melanoma were included in a retrospective analysis to determine the distance from the plaque to the tumour base using ultrasound. A phantom study was used to illustrate the effects on radiation dose to apex of the tumour when the dose depth was incorrectly determined. Doses to apex of the tumour were determined using Plaque Simulator. RESULTS: The intraobserver variation in dose depth measurement with plaque was significantly lower than for measures without plaque (p<0.001). Agreement between the surgeons was better with a plaque in place. Distances from the plaque to the tumour base were distributed with mean=0.99 (median: 1, range: 0.1-2.9 mm). From the phantom study, it was clear that the tumour did not receive the prescribed 100 Gy if the dose depth was incorrectly determined. CONCLUSIONS: The dose depth in patients with uveal melanoma must be measured accurately for correct calculation of the radiation dose to the apex of the tumour. Repeated in vivo and in vitro ultrasound measurements of dose depth showed higher variance than measurements using the mirror image produced from a ruthenium plaque. Using the mirror image thus help to improve the dose calculation.

Automatic retinal oximetry.

PURPOSE: To measure hemoglobin oxygen saturation (SO(2)) in retinal vessels and to test the reproducibility and sensitivity of an automatic spectrophotometric oximeter. METHODS: Specialized software automatically identifies the retinal blood vessels on fundus images, which are obtained with four different wavelengths of light. The software calculates optical density ratios (ODRs) for each vessel. The reproducibility was evaluated by analyzing five repeated measurements of the same vessels. A linear relationship between SO(2) and ODR was assumed and a linear model derived. After calibration, reproducibility and sensitivity were calculated in terms of SO(2). Systemic hyperoxia (n = 16) was induced in healthy volunteers by changing the O(2) concentration in inhaled air from 21% to 100%. RESULTS: The automatic software enhanced reproducibility, and the mean SD for repeated measurements was 3.7% for arterioles and 5.3% venules, in terms of percentage of SO(2) (five repeats, 10 individuals). The model derived for calibration was SO(2) = 125 - 142 . ODR. The arterial SO(2) measured 96% +/- 9% (mean +/- SD) during normoxia and 101% +/- 8% during hyperoxia (n = 16). The difference between normoxia and hyperoxia was significant (P = 0.0027, paired t-test). Corresponding numbers for venules were 55% +/- 14% and 78% +/- 15% (P < 0.0001). SO(2) is displayed as a pseudocolor map drawn on fundus images. CONCLUSIONS: The retinal oximeter is reliable, easy to use, and sensitive to changes in SO(2) when concentration of O(2) in inhaled air is changed.

Optic nerve oxygenation.

The oxygen tension of the optic nerve is regulated by the intraocular pressure and systemic blood pressure, the resistance in the blood vessels and oxygen consumption of the tissue. The oxygen tension is autoregulated and moderate changes in intraocular pressure or blood pressure do not affect the optic nerve oxygen tension. If the intraocular pressure is increased above 40 mmHg or the ocular perfusion pressure decreased below 50 mmHg the autoregulation is overwhelmed and the optic nerve becomes hypoxic. A disturbance in oxidative metabolism in the cytochromes of the optic nerve can be seen at similar levels of perfusion pressure. The levels of perfusion pressure that lead to optic nerve hypoxia in the laboratory correspond remarkably well to the levels that increase the risk of glaucomatous optic nerve atrophy in human glaucoma patients. The risk for progressive optic nerve atrophy in human glaucoma patients is six times higher at a perfusion pressure of 30 mmHg, which corresponds to a level where the optic nerve is hypoxic in experimental animals, as compared to perfusion pressure levels above 50 mmHg where the optic nerve is normoxic. Medical intervention can affect optic nerve oxygen tension. Lowering the intraocular pressure tends to increase the optic nerve oxygen tension, even though this effect may be masked by the autoregulation when the optic nerve oxygen tension and perfusion pressure is in the normal range. Carbonic anhydrase inhibitors increase the optic nerve oxygen tension through a mechanism of vasodilatation and lowering of the intraocular pressure. Carbonic anhydrase inhibition reduces the removal of CO2 from the tissue and the CO2 accumulation induces vasodilatation resulting in increased blood flow and improved oxygen supply. This effect is inhibited by the cyclo-oxygenase inhibitor, indomethacin, which indicates that prostaglandin metabolism plays a role. Laboratory studies suggest that carbonic anhydrase inhibitors might be useful for medical treatment of optic nerve and retinal ischemia, potentially in diseases such as glaucoma and diabetic retinopathy. However, clinical trials and needed to test this hypotheses.

Determinants of bleb morphology in minimally invasive, clear-cornea micropenetrating glaucoma surgery with mitomycin C.

PURPOSE: Antimetabolites, especially mitomycin C (MMC), increase the incidence of late bleb-related endophthalmitis in trabeculectomy. This is related to a higher incidence of avascular, thin, cystic, translucent blebs, which may be caused by a toxic effect on conjunctival tissue. An MMC dose-response study was carried out focusing on bleb morphology and function. PATIENTS AND METHODS: In a retrospective, comparative case series study, 2 successive groups of patients with complicated glaucoma were compared 2 years after a special, minimally invasive, filtering procedure (intrastromal holmium laser keratostomy). Preoperative local subconjunctival injections of a fixed MMC dose (4 microg) were used in group A, and lower MMC doses, calculated individually (1 or 2 microg), were used in group B. Bleb vascularity and morphology were evaluated by masked grading of photomicrographs. Bleb function was evaluated by intraocular pressure (IOP). RESULTS: Total bleb avascularity occurred in 63% of the blebs in group A and 0% in group B (P < 0.01). In eyes with IOP < or = 20 mmHg without medical treatment, the mean IOP was significantly lower in group 1 (8 vs 15 mm Hg, P < 0.002). A translucent cystic bleb without conjunctival stroma was observed in only 1 eye in group A. An optimal spongy stromal bleb was observed in all other eyes (96%) despite the different MMC doses. The numbers of complications in the 2 groups were nearly equal. CONCLUSIONS: Bleb avascularity after 4 microg MMC could be avoided by the use of 1 or 2 microg MMC on the basis of preoperative prognosticators for failure, but at the expense of some of the IOP-lowering effect. This indicates that the therapeutic index (clinical safety margin) of MMC seems to be narrow. An MMC dose-response relation was not observed for the thin, cystic, and translucent bleb. The low incidence of this bleb (4%) indicates that the operative technique, apart from the vascularity, may be the most essential determinant of bleb morphology.

Bilateral optic neuropathy in a patient with familial amyloidotic polyneuropathy.

Amyloidogenic transthyretin (ATTR)-related familial amyloidotic polyneuropathy (FAP) is an autosomal-dominant hereditary disease characterised by slowly progressive peripheral sensorimotor and autonomic neuropathy and tissue involvement of the heart, kidneys and central nervous system. Secondary glaucoma has been reported following intraocular surgery, but optic nerve involvement unrelated to glaucoma has not previously been described. We reported a male patient in his late 40s when deceased, who previously had a liver transplant in order to reduce the abnormal protein synthesis underlying his FAP ATTR Val30Met mutation. After 11 years of ophthalmic follow-up best-corrected visual acuity was 20/100 in his seeing eye, which further had visual field findings suggestive of optic neuropathy. This was also the diagnosis underlying the preceding insidious full loss of vision in the fellow eye, with colour Doppler imaging to support an ischaemic aetiology. To our knowledge, this is the first report of ischaemic optic neuropathy in this familial amyloid disorder.

A new risk-based screening criterion for treatment-demanding retinopathy of prematurity in Denmark.

OBJECTIVE: The aim of this study was to uncover the most effective and safe criterion to implement for retinopathy of prematurity screening in Denmark. METHODS: This retrospective national cohort study is based on data from 3 national registers. These registers provided on infants treated for retinopathy of prematurity, infants in need of treatment but missed by the present screening program, and the candidate neonates for advanced retinopathy of prematurity development A nonlinear logistic regression model was fitted to the data, and various screening criteria were evaluated. RESULTS: During the study period (2002-2006), 116 infants were treated for retinopathy of prematurity, no treatment-demanding retinopathy of prematurity infants were missed by the screening program, and 182 premature infants were candidates for developing treatment-demanding retinopathy of prematurity. Screening criteria combining gestational age at delivery and birth weight limits and new risk-based criteria were compared with regards to their effectiveness. The risk-based criteria were the most effective. Use of the 0.13% risk-based criterion to define the population to be screened resulted in the detection of all treated infants in the study period and 17.4% fewer infants to screen. The model predicted this criterion to result in 1 missed case of treatment-demanding retinopathy of prematurity every 11 years and 1 case of blindness every 18 years in Denmark. CONCLUSIONS: Screening criteria based on risk estimates of developing treatment-demanding retinopathy of prematurity are the most effective for retinopathy-of-prematurity screening. The risk-based criterion of 0.13% can safely be implemented for future retinopathy-of-prematurity screening in Denmark.

Treatment for retinopathy of prematurity in Denmark in a ten-year period (1996 2005): is the incidence increasing?

OBJECTIVE: The objective of this study was to analyze the population incidence of retinopathy of prematurity treatment in Denmark in the 10-year period from 1996 to 2005. METHODS: Patient charts of infants treated for retinopathy of prematurity and the national birth registry provide information about neonatal parameters. These parameters, along with birth in the latter half of the period (2001-2005), were analyzed as risk factors for retinopathy of prematurity. The national registry for blind and visually impaired children was accessed to obtain information about visual impairment attributable to retinopathy of prematurity in both treated and untreated infants. RESULTS: The study population consisted of 5467 Danish preterm infants born in 1996 to 2005, with a gestational age of < 32 weeks, who survived for > or = 5 postnatal weeks; 2616 were born in 1996 to 2000, and 2851 were born in 2001 to 2005. The incidence of treated retinopathy of prematurity cases increased significantly from 1.3% in 1996 to 2000 to 3.5% in 2001 to 2005. Significant risk factors for retinopathy of prematurity treatment were low gestational age, small for gestational age, male gender, and multiple birth. Other, yet unknown factors contributed to the increased incidence in the latter half of the period. Of the study population, 0.6% were registered as visually impaired because of retinopathy of prematurity within 2 years after birth (early-detected visual impairment). The incidences were not significantly different between 1996 to 2000 and 2001 to 2005. Of all of the early-detected, visually impaired children, 16% had not been treated for retinopathy of prematurity and were considered screening failures. CONCLUSIONS: The incidence of retinopathy of prematurity treatment in Denmark has more than doubled during the past half-decade. This increase could not be fully explained by increased survival rates for the infants or by changes in the investigated neonatal risk factors.

A comparison of colour micrographs obtained with a charged couple device (CCD) camera and a 35-mm camera.

PURPOSE: The purpose of this study was to determine if micrographs produced with a colour charged couple device (CCD) camera were comparable in quality to micrographs obtained with a 35-mm colour film camera. The Axiocam (Zeiss, Jena, Germany) CCD camera produced images of 3900 x 3090 pixels. METHODS: Each picture in a series of 50 pairs of film and digital micrographs was rated independently by each of three observers on the categories of colour, detail and overall impression. A total of 28 of the 50 pairs of micrographs were discarded due to colour differences. RESULTS: Digital micrographs were rated lower on colour and higher on detail compared to film micrographs. The film and digital micrographs were rated equally on overall impression. The difference in colour between film and digital micrographs can be compensated for using image processing software on the digital image. However, such manipulation was not carried out as part of the present study. The study originally included 50 digital micrographs and 50 film micrographs. The micrographs were paired and 22 of the 50 pairs of micrographs were assessed. Thus 28 pairs were not evaluated due to colour differences in the non-manipulated pictures. The interobserver difference on colour in the remaining 22 pairs given as mean square +/- standard error of the mean was - 0.27 +/- 0.10, 0.62 +/- 0.10 and 0.90 +/- 0.11. The interobserver difference on detail was - 0.48 +/- 0.10, 0.95 +/- 0.10 and 1.43 +/- 0.10. The interobserver difference on overall impression was - 0.70 +/- 0.10, 0.57 +/- 0.10 and 1.27 +/- 0.10. All the results differed significantly (p < 0.001). CONCLUSION: Digital micrographs are sufficient in detail, colour and overall impression to replace the traditional 35-mm film recordings for use in histopathology.

Uveal effusion and ultrasonic imaging: a clinical series.

PURPOSE: To establish the diagnostic role of imaging by ultrasound for the diagnosis of uveal effusion syndrome. METHODS: Using ultrasonic imaging features as the main criteria for evaluation, the recorded data from 16 patients with presumed uveal effusion seen between 1994 and 2000 were reviewed and analysed for clinical manifestations and current diagnostic suggestions. Eventually, as cumulating experience suggested that ultrasound is capable of indicating uveal effusion, the study set-up became in part more prospective. RESULTS: The two main ultrasonic features found were: (1) extended multi-layered detachment patterns by B-scan, often kinetically mobile; (2) a spongy oedematous ciliary body region, often with interstitial lacunae, as demonstrated by high-resolution ultrasound biomicroscopy (50 Mhz). CONCLUSIONS: In patients with visual loss and ambiguous detachment-like fundus pathology, ultrasonic features are often of practical guidance for diagnosing uveal effusion syndrome.