A computer-based register for inherited retinal dystrophies in Southern Africa

A genetic register for inherited retinal degenerative disorders (RDDs) has been established at the Division of Human Genetics, UCT Medical School, Cape Town, South Africa. The primary role of the register is to monitor the progress of molecular research and to facilitate the efficient delivery of services, including genetic counselling, to respective family members and new patients. The database currently holds information on 1829 subjects. The RDD-specific breakdown of the data are presented.     

Evaluation of heredity as a determinant of retinal nerve fiber layer thickness as measured by optical coherence tomography

PURPOSE: To study to what extent genetic factors determine the retinal nerve fiber layer thickness (RNFLT) in healthy subjects. METHODS: In vivo peripapillary optical coherence tomography (OCT), clinical examination, lens fluorescence, and fundus photography were performed on both eyes of 25 monozygotic and 25 dizygotic same-sex pairs of twins. The cross-sectional study included twins aged from 20 to 45 years recruited from a population-based register. Only healthy eyes were included. Main outcome variables: peripapillary OCT RNFLT, reproducibility, and heritability (the proportion of the total observed variance statistically attributable to genetic factors). RESULTS: The within-pair difference in RNFLT was 4.6% (0.7%-15.2%; median [range]) in monozygotic versus 7.3% (0.2%-20%) in dizygotic twins (P = 0.032, Mann-Whitney test). The RNFLT heritability was 66%. The RNFLT measurement was found to decrease 3.8 microm per decade (P = 0.003). The RNFLT heritability increased to 82%, when corrected for the effect of age and excluding within-pair refractive differences of 2 D or more. The signal-to-noise ratio correlated with lens transmittance (r = 0.25, P = 0.012), age (r = -0.29, P = 0.004), and RNFLT (r = 0.43, P < 0.001). Intravisit RNFLT reproducibility was 4.2%. CONCLUSIONS: Peripapillary RNFLT in healthy adults, as measured by OCT, was determined predominantly by genetic factors in this study population. Theoretically, these factors may involve variations in the number of ganglion cells and nerve fiber formations early in life and/or in the rate at which these structures are subsequently lost.     

Adding screening for “end organ damage” to the noncommunicable disease package in primary care

There are several global and local initiatives aimed at screening for noncommunicable diseases (NCD). The fundamental health system strengthening to achieve this goal is by developing the primary care infrastructure. Most newly developed or improved primary care centers focus on maintaining an NCD register for onward reporting. However, the register is also the cornerstone for implementing systematic screening of all complications of NCDs. With epidemiologic transition, end organ damage due to NCDs is one of the most common causes of morbidity and mortality. Screening for end organ damage and early identification of treatable complications are far more impactful than waiting for self-reported symptomatic complications. Here, we show an example of how the Government of Kerala utilized the NCD register to implement a systematic diabetic retinopathy screening that allows for annual or biennial re-call in the primary care and refer treatable eye conditions to secondary care. The success of this program enabled the Government to initiate a holistic approach to screen for other complications of diabetes.     

Assessing the diagnostic validity of a blind register

Background: To validate the accuracy of clinical ophthalmic information held on the West Australian blind register. Design: Community‐based cross‐sectional study. Participants: Legally blind or severely vision‐impaired people were selected randomly from the Association for the Blind of Western Australia register. Methods: Individuals were reviewed by one of two consultant ophthalmologists. Main Outcome Measures: The positive predictive value (ppv), sensitivity and specificity for legal blindness status and diagnostic causes of vision loss were calculated using data extracted from the Association for the Blind of Western Australia blind register. Results: 273 blind or near blind people were reviewed from the register total of 4271 individuals. There were more women (57%) than men, median age 81 years. For legal blindness status the ppv was 0.88 (95% confidence interval [CI] 0.82–0.92), sensitivity 0.75 (95% CI 0.74–0.84) and specificity 0.6 (95% CI 0.46–0.73). The ppv for the diagnostic causes of blindness were: age‐related macular degeneration = 0.95 (95% CI 0.91–0.97), retinitis pigmentosa ppv = 1 (95% CI 0.81–1.0), diabetic retinopathy ppv = 0.9 (95% CI 0.57–0.99), optic neuropathies ppv = 0.77 (95% CI 0.51–0.92) and glaucoma ppv = 0.87 (95% CI 0.7–0.96). Forty individuals (15%) had treatable conditions contributing to their vision loss. Conclusions: The blind register diagnoses and legal blindness status are of high accuracy. This information allows useful linkages to other databases for studies of blindness interactions. A regular updating mechanism would improve the future accuracy of this valuable regional asset. The presence of untreated cataract suggests that regular follow up and appropriate treatment may help optimize vision in blind patients.     

Trends in blind registration in the adult population of the Republic of Ireland 1996-2003

BACKGROUND/AIM: The Republic of Ireland has a centralised database of all registered, blind people in the country. The last study of the national blind register was undertaken in 1996. The current study sought, firstly, to investigate and identify any recent changes in the register composition. Secondly, there is concern that many eligible people are not appropriately registered. To examine this further, registration levels among patients attending an Irish outpatient ophthalmology clinic were determined. METHODS: Criteria for blind registration in Ireland are (1) a best corrected visual acuity of 6/60 or less in the better eye, or (2) a visual field subtending an angle of 20 degrees or less. The National Council for the Blind in Ireland (NCBI) is the sole custodian of a national registration database recording all eligible, registered people. This computerised database was analysed to provide information on the demographics and blind registration condition of those on the register in 2003. This information was compared with the results of the 1996 study. To assess the accuracy of the current register, the registration status of eligible patients attending the outpatient clinic of a busy, tertiary referral ophthalmology department, over a 9 week period, was studied. RESULTS: 6862 adults were registered as blind on the NCBI register in Ireland in 2003, representing an increase of 37% since 1996. The leading causes of registration were age related macular degeneration (ARMD) (25%), glaucoma (12%), and retinitis pigmentosa (7%). Comparing the 1996 and 2003 data, dramatic increases in the numbers registered caused by ARMD (from 812 to 1729 people, a 113% increase) and diabetic retinopathy (DR) (from 147 people to 323 people, a 120% increase) were found. The numbers registered as a result of glaucoma were relatively stable (795 in 1996 and 811 in 2003). A substantial drop, of 53%, was noted in the number of people registered as a result of cataracts, from 561 people to 261. Of the 672 new cases registered in 2003, ARMD accounted for 44%, glaucoma 13%, and DR 7%. Over the 9 week study period 75 patients, out of a total 2320 patients who attended the outpatient department, fulfilled the blind registration criteria. It was found that 21% (16 of 75) of the eligible clinic outpatients had not been appropriately registered. CONCLUSION: An overall increase in adult blind registration of 37% in the Republic of Ireland was found between 1996 and 2003. There were large increases in registered blindness as a result of ARMD (113%) and DR (120%). A notable decrease in registration as a result of cataracts was discovered. Vigilance by clinicians is necessary to ensure that eligible patients are registered.     

Intraoperative corneal topography for image registration

PURPOSE: To present a method to measure the three-dimensional shape of the cornea and to use the data for registration purposes in order to optimize ablation pattern alignment during corneal laser surgery. METHODS: The three dimensional shape of the cornea can be measured with a modified fringe projection technique using UV laser pulses. A method to register these shape images is presented. The registration is done via established algorithms that use peripheral elevation data, which is not affected during the laser treatment. The method also provides a means to control the absolute amount of tissue removal. The three-dimensional registration method is compared with conventional two-dimensional eye tracking. RESULTS: Due to the parallax of the cornea with respect to the pupil center, considerable decentration of laser ablation patterns can occur when tracking just the pupil center. Registration using three-dimensional shape measurements provides a more accurate means to control ablation pattern application. CONCLUSIONS: A new method to register corneal shapes is discussed. It should allow monitoring the real ablation rate online during the treatment and might eventually serve as an online feedback system to control the laser ablation-induced corneal shape changes.     

Causes of blindness and partial sight in the Bradford Metropolitan District from 1980 to 1985

A retrospective review of the BD8 forms submitted for the period 1980-85 in the Bradford Metropolitan District was conducted to ascertain the incidence and causes of blindness and partial sight. A total of 1485 cases were registered in this period of which 755 (50%) were included in the Blind register and 730 (49.2%) in the Partially Sighted register. Age-related macular degeneration was the most important cause of visual handicap, accounting for 43.9% of all registrations, followed by glaucoma (16.2%), diabetic retinopathy (6.3%), myopic degeneration (6.1%), optic atrophy (4.4%), cerebrovascular disease (3.8%), cataracts (3.6%), retinal vascular occlusive disease (3.2%), corneal opacities (3.0%), congenital anomalies (2.7%), retinitis pigmentosa/tapeto-retinal degeneration (1.9%), retinal detachment (1.8%) and others (3.1%). The ratio of female to male registrations was 1.8:1. Eighty-four per cent of this sample population was above the age of 60 years at the time of registration.     

Stereoscopic fluorescein angiography of the fundus

The fundus of the eye is a three-dimensional organ. The usual two-dimensional representation of the angiogram provides us with incomplete information. It is true that it is usually possible by indirect means to deduce at which level the pathological process is taking place, but a simple technique enables one to register and project the angiogram stereoscopically. This gives the observer a direct visual impression of the spatial proportions of the pathological process.     

Molecular basis for photoreceptor outer segment architecture

To serve vision, vertebrate rod and cone photoreceptors must detect photons, convert the light stimuli into cellular signals, and then convey the encoded information to downstream neurons. Rods and cones are sensory neurons that each rely on specialized ciliary organelles to detect light. These organelles, called outer segments, possess elaborate architectures that include many hundreds of light-sensitive membranous disks arrayed one atop another in precise register. These stacked disks capture light and initiate the chain of molecular and cellular events that underlie normal vision. Outer segment organization is challenged by an inherently dynamic nature; these organelles are subject to a renewal process that replaces a significant fraction of their disks (up to ∼10%) on a daily basis. In addition, a broad range of environmental and genetic insults can disrupt outer segment morphology to impair photoreceptor function and viability. In this chapter, we survey the major progress that has been made for understanding the molecular basis of outer segment architecture. We also discuss key aspects of organelle lipid and protein composition, and highlight distributions, interactions, and potential structural functions of key OS-resident molecules, including: kinesin-2, actin, RP1, prominin-1, protocadherin 21, peripherin-2/rds, rom-1, glutamic acid-rich proteins, and rhodopsin. Finally, we identify key knowledge gaps and challenges that remain for understanding how normal outer segment architecture is established and maintained.     

No increased risk of developing Alzheimer disease in patients with glaucoma

PURPOSE: To investigate whether primary open-angle glaucoma (POAG) is associated with increased risk of developing Alzheimer disease (AD). METHODS: In a nationwide case register linkage study of patients with hospital admission or outpatient contact during the period from 1977 to 2001 in Denmark, the rate of subsequent AD for patients with a diagnosis of POAG was compared with the rate for patients with primary angle-closure glaucoma (PACG), cataract, and osteoarthritis (OA) and with the rate for the general population. RESULTS: A total of 11,721 patients with a diagnosis of POAG (including normal tension glaucoma), 5975 patients with PACG, 162,640 patients with cataract, and 230,208 patients with OA were identified in the registers. Patients with POAG did not have increased rate of subsequent AD compared to patients with PACG, cataract, or OA or compared with the general population. CONCLUSIONS: POAG was not associated with increased risk of developing AD. It cannot be excluded that this negative finding is due to diagnostic misclassification as register data were used.     

German register for glaucoma patients with dry eye. I. Basic outcome with respect to dry eye

Background  The purpose of this register was to determine the links between glaucoma, age, concomitant disease, medication, and dry eye in a large group of glaucoma patients. Methods  A total of 20,506 patients from 900 centers across Germany were included. The first 30 consecutive glaucoma patients at each center were recruited. Epidemiological data as well as information on glaucoma, medication, concomitant diseases, dry eye, and local symptoms were elicited by means of a questionnaire. We analyzed primary open-angle glaucoma (POAG), pseudoexfoliation glaucoma (PEX), and pigmentary glaucoma (PDG). Results  According to the register data, more women develop dry eye and glaucoma than men (56.9 vs. 45.7%). The most frequent concomitant systemic diseases were hypertension (48.1%), diabetes mellitus (22.5%), and dry mouth, nose, and skin (11.3%). As expected, the highest incidence of dry eye was found in those patients with dry mouth, nose, and skin. Dry eye occurred with dissimilar frequencies in association with the various glaucoma types: PEX>POAG>PDG. The incidence of dry eye increases with age. The gender difference in the occurrence of dry eye becomes apparent from the age of 50. Dry eye occurred more frequently when three or more antiglaucoma drugs were used and increased with the duration of glaucoma disease. Conclusions  We publish the first results from the German Glaucoma and Dry Eye Register. We found that the occurrence of dry eye is linked to several factors. Thus, the type of glaucoma has an impact on the risk of dry eye. The quantity of eye drops applied also plays a role in the development of the dry eye syndrome if more than three medications are used. While POAG is usually treated with one drug, PEX and PDG tend to be treated with multiple drugs. The gender difference in the occurrence of dry eye becomes apparent from the age 50 years. Because of the vicious circle of dry eye, antiglaucoma eye drops containing benzalkonium chloride compromises patient compliance. The results of the register are therefore of key relevance for the care of glaucoma patients. Sponsoring organizations: Chibret Pharmazeutische GmbH     

A new instrument for measuring eyelid strength

Former investigations concerning muscular eyelid strength with dynamic registration revealed great inter- and intraindividual variations. We tried to minimize these influences by using an electronic power register with isometric registration. This is important because lid closing is a complex mechanism of horizontal and vertical movements with continuously changing power vectors. Our new apparatus reduces false results. A normal collective of 114 persons was examined. The results show no statistically significant age- or sex-related differences in lid strength.     

Klinische und neuroradiologische Diagnostik bei endokriner Orbitopathie

Early diagnosis of Graves' orbitopathy (GO) is important for a timely treatment of the disease. The diagnosis is based on clinical as well as radiological findings. Detailed assessment and follow-up mainly rely on standardized clinical examinations which register symptoms and signs including inflammation, upper lid retraction, exophthalmos, eye muscle involvement and diplopia, corneal involvement, raised intraocular pressure and optic nerve involvement, the latter representing a particular challenge. Each case of GO is classified in terms of severity and activity allowing suitable therapeutic strategies to be derived.     

The relationship between two types of upper eyelid movements: saccades and pursuit

PURPOSE: To establish the relationship between upper eyelid saccades and upper eyelid pursuit movements. METHODS: Upper eyelid saccades and periodic sinusoidal upper eyelid pursuit movements were recorded in a sample of controls and patients with Graves upper eyelid retraction. A video-computerized system was used to register both types of movements that accompanied 60 degrees of eye rotation across the upper and lower hemifields. The forced harmonic oscillator model was used to fit saccadic and pursuit movements. RESULTS: Mean mid-pupil eyelid distance for the Graves patients (6.6 +/- 1.1 mm) was significantly higher than for the controls (4.6 +/- 0.8 mm; t = 7.18; P < 0.00001). Despite the difference in the upper eyelid resting position, saccades and pursuit eyelid movements of both groups were extremely well fitted by underdamped solutions and steady forced solutions of the harmonic oscillator model, respectively. For the controls, the amplitude of the pursuit movements was well correlated with the upward and downward saccades. The amplitude of the eyelid movements of the Graves patients (saccades and pursuit) was significantly reduced compared with that of the controls. CONCLUSIONS: Saccadic and pursuit movements of the upper eyelid can be described by the harmonic oscillator model. In healthy subjects and Graves patients, the amplitude of pursuit lid movements is correlated to the saccade amplitude. Pursuit eyelid movements are more difficult to register than saccades, and their measurements do not allow clear separation of the relaxation and contraction properties of the upper eyelid retractors.     

Survival of elderly ophthalmic out-patients

Elderly ophthalmic out-patients that had visited an eye-clinic were searched in a population register 7 years later. Observed numbers of survivors were compared with those expected according to appropriate life tables. Most observed numbers of survivors came close to the expected ones. Patients, aged more than 80 years when visiting the eye-clinic, had, however, a consistently increased survival rate. Glaucoma patients, less than 80 years old, had a slightly (not significantly) lower survival rate than expected.     

Sussex Eye Hospital sports injuries.

To assess the prevalence of sports eye injuries in our area a register was kept over the 18 months from October 1982 to March 1984. Squash, association football, badminton, and tennis were the main offenders. The severest injury was from a golf ball, involving a fractured zygoma. There was one retinal dialysis, and one lens dislocation requiring extraction. Spectacles were broken in six cases and a contact lens in one. Glass fragments needed operative removal in one case, but there were no penetrating injuries. The value of eye protection, not worn by any of our patients, is emphasised.     

Association of ocular pseudoexfoliation syndrome with ischaemic heart disease, arterial hypertension and diabetes mellitus

Purpose: To determine the prevalence of pseudoexfoliation syndrome (PEX) in Lithuanian urban population and its association with ischaemic heart disease (IHD), arterial hypertension (AH) and diabetes mellitus (DM). Methods: In this population-based study, 1065 participants aged 45-72?years were randomly drawn from the population register of Kaunas, Lithuania. They were classified as having PEX if any pseudoexfoliation material was determined by a slit-lamp examination in at least one eye. The data were acquired from questionnaire; register of myocardial infarction, electrocardiogram, biochemical blood analyses and blood pressure measurement were used to determine IHD, AH, DM and smoking habits. Poststratification weights based on Kaunas population sex and age distribution were applied. Results: Pseudoexfoliation syndrome was estimated in 9% of a population. The AH rate was higher in PEX subjects than in non-PEX subjects (p?=?0.017) and the rates of IHD, DM and cholesterol levels did not differ statistically significantly. Chi-square linear-by-linear association test found higher AH rate in unilateral PEX subjects and even higher AH rate in bilateral PEX subjects than in non-PEX subjects (p?=?0.014). Pseudoexfoliation syndrome increased odds for AH by 1.8 times (p?=?0.021). Median of systolic blood pressure was higher in the PEX group than in non-PEX group (p?=?0.04). But all associations could not be confirmed after adjusting for age. Smoking duration increased age-adjusted odds for PEX. Pseudoexfoliation syndrome did not increase risk for IHD, AH or DM. Conclusions: Pseudoexfoliation syndrome prevalence is high in Lithuania. No clear PEX association with IHD, AH and DM was proven after controlling for effect of age.     

Measurement of the mechanical stiffness in cyclotorsion of the human eye

We have measured the stiffness in cyclotorsion of the human eye using a scleral suction contact ring mounted on a shaft fitted with an eddy current motor to provide the torque to turn the eye and a shaft-position-encoder to register the torsion. The relation proved to be almost linear within the measuring range in four subjects with constant slope values of about 0.75, 0.60, 0.55 and 0.45 g·cm/deg. The average, 0.6 g·cm/deg, equals 0.5 g if applied at the radius of the globe. This value is rather low compared to the values obtained by other authors for horizontal eye movements. This may be due to different length-tension characteristics of oblique muscles compared to recti muscles.