Prevalence of Pseudoexfoliation among Adults and its Related Ophthalmic Variables in the Community of Kebena Woreda, Gurage Zone, Ethiopia

Clinical studies in the hospital settings using patients having ocular morbidities have shown a high prevalence of pseudoexfoliation (PXF) in Ethiopia. With this information in mind community based study was conducted to determine age and sex-specific prevalence of pseudoexfoliation syndrome (PXF) and its relationship with some ophthalmological variables.Objective To determine the prevalence and clinical features of pseudoexfoliation among adults in kebena woreda of Gurage zone, SNNPR, Ethiopia.Design Random cross-sectional samples of adult population aged 40 years or older in the community of the district.Methods A total of 760 subjects aged 40 years or older underwent standardized examination, including portable slit lamp biomicroscopy before and after pupillary dilatation, and IOP measurement using Tono-Pen. PXF was diagnosed on slit lamp exam by the presence of white dandruff-like material on the pupillary margin and/or on the anterior lens capsule of one or both eyes.Results Among 760 participants, the prevalence of PXF was 12.0% (95% confidence interval, 9.7%-14.3%). The mean age was 63.9 years (SD 9.96, age range 40-90 years). Fifty six percent were found to have bilateral PXF. The prevalence increased with increasing age, with 26.9% of those 60 or older affected. Slightly higher proportion of males (12.4%) were found to have pseudoexfoliation in either of the eyes than females (11.6%) which was not statistically significant (p=0.738). Mean IOP in subjects with PXF was found to be 20.65 + 5.15 mmHg, while it was 15.0 + 2.3mmHg for those without PXF. The difference between the two populations was found to be statistically significant (P<0.05).Conclusions The prevalence of PXF in eyes of people in Kebena appears greater than that reported in other places of Africa and Asia. PXF occurs at a

relatively younger age in our population. Increasing age is associated with the presence of PXF, and PXF in turn is associated with high IOP. Background Pseudoexfoliation (PXF) is characterized by the accumulation of extracellular fibrillar material in many ocular and systemic tissues (1) and is often associated with glaucoma (2).
Pseudoexfoliation is an age-related syndrome with wide geographic variations in prevalence (3)(4)(5)(6)(7)(8)(9), even within the same population (7). The differences in prevalence have not been well explained. These variations may be either a true biological, ecological, or may even be differences related to examination techniques and diagnostic abilities.
A high prevalence of PXF in a developing country, with a large proportion of blindness due cataract and glaucoma is important for three reasons. The first is that pseudoexfoliation is associated with weak zonules and an increased risk for complications during cataract surgery (10), secondly; a clinical observation of PXF may be used as a marker to identify an individual at risk of glaucoma. Finally, an association between pseudoexfoliation and angle-closure glaucoma (10,11) has been found in some ethnic groups and PXF may act as a marker to identify those with this form of glaucoma.
Clinical studies in hospital settings in Ethiopia using patients having ocular morbidities have shown high prevalence of PXF (12)(13)(14). A recent unpublished hospital based study suggested that pseudoexfoliative glaucoma as the second most common cause of chronic glaucoma in 37% (14). No population based prevalence studies of PXF have been published from Ethiopia. A study in South Africa revealed a prevalence of 0.08% in adults over the age of 40 (15). It is unclear whether the general population in Ethiopia has a high prevalence of PXF.
This study aimed to determine the prevalence of pseudoexfoliation in a community in southern Ethiopia among adults of 40 years and older and identify its relationship to some ophthalmic variables Methods This was a cross sectional Community based study that was conducted in Kebena woreda of the Gurage Zone, Ethiopia, from January 2017 to February 2017. This district is located 155 Kilo meters from Addis Ababa and consisted of 23 kebeles.
The total population of the area was 70,839 for the year 2017. There were estimated 14,000 households and the mean household size was 5 people. The study population was Residents of Kebena district who were 40 years and older.

Sample size Calculation
Using a prevalence of 0.08 (taken from the population-based study in South Africa) (15) , a margin of error of 2%, and a confidence limit of 95% and a non response rate of 15% , a sample size of 784 was established.

Sampling technique
Multi stage sampling with probability proportionate to size was employed to select the sample. Kebeles were taken as first stage sampling units. A kebele is the smallest administrative unit of Ethiopia. Each kebele consists of at least five hundred families, or the equivalent of 3,500 to 4,000 persons. It is part of a woreda.
The list of current kebeles in the woreda was obtained from the local administration and a random sample of 10 kebeles was taken from all the 23 kebeles in the Woreda. Households in each of the selected kebeles served as second stage units. A household constitutes a person or group of persons, irrespective of whether related or not, who normally live together in the same housing unit or group of housing units and who have common cooking arrangements. A systematic random sampling was used to select the sampling units. The total sample size calculated for the district was distributed for the kebeles based on their population size; sample allocation using probability proportional to size (PPS) technique. The sampling interval was subsequently calculated using the number of households in the 10 Kebeles divided by the required number of households (i.e.6025/784=7) and the starting point (sampling unit) was determined using lottery method. Every seventh household was then eligible for inclusion.
One individual above the age of 40 was eligible for examination from each of the selected households and a Lottery method was used when there were more than one individual in the selected households.

Data collection method
Each eligible household was visited, and a study subject selected.
Sociodemographic data were filled in the questionnaire and visual acuity of both eyes separately was assessed outside the house in a shaded area. Visual acuity was measured using tumbling-E Snellen chart, and whenever the Visual Acuity was found to be worse than 6/9, a pin hole was used to account for possible refractive error.
Both eyes of all subjects were examined using a portable slit lamp before and after pupillary dilatation for signs of PXF in the anterior segment. PXF was diagnosed on slit lamp biomicroscopy by the presence of white dandruff-like material at the pupillary margin and/or on the anterior lens capsule of one or both eyes. Intraocular pressure (IOP) was measured using Tono-Pen (Medtronic Solan, XL) before pupillary dilation. In order to estimate the width of the chamber angle, Van-Herrick method was used and when the drainage angle was judged to be not occludable (the distance between the anterior surface of the iris and the posterior surface of the cornea is more than one-fourth the corneal thickness), the pupils were dilated with 1% Tropicamide and 2.5% Phenylephrine hydrochloride to allow examination of the lens. WHO Simplified Cataract Grading System was utilized to document about the status of the lens (17). Cataract was said to be present when nuclear, Cortical, or Posterior subcapsular standards were 2 and above. Subjects having Corneal opacification dense enough to obscure visualization of the anterior segment, evidence of active or past attack of anterior uveitis, or a history of intraocular surgery for cataract, glaucoma, or retinal detachment were excluded. Best villagebased visual acuity was defined as the better of presenting and pinhole visual acuity, as measured during data collection.

Statistical analysis
Data was entered into a computer and edited for any inconsistencies before analysis using SPSS for Windows Version 15.0 to calculate means, cross tabulations and x 2 tests. Odds ratios were used to assess the odds of having increased IOP with and without PXF. Associations between PXF, demographic factors, and, other ocular diseases were computed using either the x 2 or Fisher exact test, and P-values below 0.05 were considered statistically significant. Odds ratios were calculated, separately for right and left eyes, to test for associations between pseudoexfoliation and IOP, and pseudoexfoliation and senile lens changes.

Results
A total of 760 subjects were examined, giving a response rate of 96.8%. Three hundred fifty-five (46.7%) were males and 405(53.3%) were females. The mean age was 54 (SD 9.74) (range 40-90) years. Table 1 shows the age and sex distribution of the study subjects. Slightly higher proportion of males (12.4%) were found to have pseudoexfoliation in either of the eyes than females (11.6%) which was not statistically significant (p=0.738), even after Standardization for age differences (p=0.317; age adjusted odds ratio, 1.29; 95% confidence interval, 0.79 to 2.11).

Features of PXF
In 68 eyes (47.2%), deposits were visible only at the pupillary border, while in 14  Cataract was found in 59.2% of eyes with PXF, but in only 13.5% of Non-PXF eyes (p < 0.001), indicating a strong association between cataract and PXF. Table 3 presents data on the association between pseudoexfoliation and senile lens changes for right and left eye. In a univariate analysis nuclear and posterior subcapsular cataract were found to be significantly associated with pseudoexfoliation. (p=0.03) But when adjusted for age, the association becomes statistically insignificant.  (7), and 38% in Navajo Indians (18).
This finding therefore suggests both genetic and environmental influences even though differences in prevalence across populations need to be interpreted with caution considering the difficulties and lack of standardization in diagnosis and the potential for sub clinical or early cases to be missed.
Two hospital-based published reports from Ethiopia described a high prevalence of PXF amongst patients with glaucoma or ocular hypertension (25.0%) (12) and cataract (39.3%) (13). However, this is the first population-based survey of the prevalence of PXF in Ethiopia. This study confirms the high prevalence of PXF in Ethiopia.
We found that the mean age of subjects with PEX syndrome is 11.27 years older than the normal population. Considering age specific prevalence rates, there was a significant linear increase in prevalence with age. This is also in agreement with previous reports that have shown that the prevalence of PEX increases with advancing age (4)(5)(6)(7)(8)(19)(20)(21)(22)(23)(24).One remarkable finding in our results is that PXF occurs at a relatively younger age in our population (mean age being 63.9 years (SD 9.96, age range 40-90 years) compared to studies done in Iceland (mean age of 72) (24) and the Framingham study (19).This is also in agreement with findings in a hospital based study in Ethiopia (13) , which has reported a mean age of 63.7 ± 10.7 years (range 47-91 years) in patients with PXF who were scheduled for cataract surgery. It has been suggested that persons living in lower latitudes appear to develop PEX at younger age (25). Bartholomew RS (1973): reported a prevalence rate of 6.4% in the 30-39 years age group among the Bantu of South Africa (26).This finding could support the theory of genetic predisposition and environmental effects in the development of PXF even though the well-known difficulty of determining age in a largely illiterate community has to be acknowledged in our study.
There are conflicting reports of gender differences in the prevalence of PXF. Women were found to be more frequently affected than men in Reikjavik eye study of Iceland and the Framingham eye studies. On the contrary, studies in Greece (20), Iran (23), and Turkey (27) have shown the reverse. We found the prevalence of PXF among men to be marginally higher than in women, but the difference was not statistically significant, which is in accordance with the findings of south Indian study (28). Probably climatic conditions provoke more or less equally intense effect in both groups of populations because females spend more of their working time in the farm land helping their husbands with farming in the district.
The finding that a reasonable number of participants with pseudoexfoliation have clinically visible deposits only over the surface of the lens emphasizes the need for dilated lens examinations preoperatively.
Like many of population based studies (20,21,22,29), we found IOP levels to be generally higher in eyes with pseudoexfoliation than in eyes without it. The mean IOP in subjects with PXF was 5.27 mm Hg higher than in those without PXF which was significant.
High IOP (IOP>21mmHg) was recorded in 36.1% of subjects with PXF compared to 0.8% in subjects without PXF. The PXF population had a significantly increased prevalence of IOP over 21 mmHg. Although investigation for evidences of glaucoma is beyond the scope of this study, it seems that a significant number of subjects with PXF were found to have one of the major identified risk factor for glaucoma, i.e. ocular hypertension.
The increasing prevalence of PXF and cataract with age and the association of PXF Further studies are recommended to scrutinize the reason why relatively younger adult are affected more frequently in our population and identify the cause of poor vision in patients with PXF, review the relationship between PXF and glaucoma in our population, and identify the conversion rate of unilateral PXF to bilateral PXF and development of ocular hypertension over a certain period of time.

Declarations
Ethical approval and consent to participate The study was conducted following the Kelsinki declaration and after it was approved by the research ethical committee of School of Medicine, Addis Ababa University. Informed verbal consent was taken and only those who consented were studied.

Consent for Publication
The manuscript represents original and valid work and that neither this manuscript nor one with substantially similar content under our authorship has been published or is being considered for publication elsewhere, except as described in the journal's submission form and cover letter submitted with the manuscript, and copies of closely related manuscripts have been provided. We agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved; and If requested. All identifying information of subjects involved in the study has been appropriately anonymized.

Availability of data and material
We will provide the data or will cooperate fully in obtaining and providing the data on which the manuscript is based for examination by the editors or their assignees; and I, as the corresponding author, agree to serve as the primary correspondent with the editorial office, to review the edited manuscript. Figure 1 Distribution of PXF by age among adults in Kebena Woreda, Gurage zone, January 2017