Ethics approval consistent with the tenets of the 1964 Declaration of Helsinki was obtained from Ethics and Research Committee of LUTH (ADM/DCST/HREC/Vol. XVI/APP/765).
2.6. Study Procedure
The study comprised two stages. Stage 1 was the establishment of the diagnosis of glaucoma. Distance visual acuity was tested using a Snellen chart or tumbling E chart placed 6 meters from the participant. Visual acuity was classified based on the WHO classification of visual impairment and blindness  . Under this classification, vision is classified as normal vision, moderate visual impairment, severe visual impairment and blindness.
A pen light was used to assess pupillary response. The iris was examined with a slit lamp biomicroscope. The intraocular pressure (IOP) was measured using a slit lamp biomicroscope with an attached Haag-Streit Goldmann applanation tonometer. Central corneal thickness measurement was done using the Alcon Ocuscan RxP ultrasonic pachymeter, S/N 100246010IX. Herndon’s formula was utilized for the calculation of true IOP  . The pupil was dilated using 1% tropicamide. The posterior segment was examined using a +78D Volk lens indirect slit lamp biomicroscope.
Ocular perimetry was done to confirm glaucoma in those with suspicious discs using the central visual field (CVF) perimeter (Zeiss Humphrey Matrix FDT). A reliable result was expected to have fixation losses < 20%, false negatives < 33% and false positive < 33%. The mean deviation of the most reliable CVF was coded and recorded. Only eyes with visual acuity > 3/60 were suitable for CVF. Those with IOP > 21 mmHg, with other features suggestive of glaucoma, were regarded as high tension glaucoma patients. However, those with IOP > 21 mmHg without features suggestive of glaucoma were regarded as ocular hypertensive patients and were excluded from the study.
In Stage 2, following diagnosis of glaucoma, patients were given an appointment within one week for examination of the eye for pseudoexfoliation and subsequent treatment. The patients to enter Stage 2 were selected by simple random sampling through balloting. The study proforma was used to obtain bio-demographic information, relevant medical and social history. All patients underwent a fasting blood sugar measurement (FBS) and 2-hour postprandial test (2 HPP), done using a glucometer. Those with fasting blood sugar (FBS) > 7.1 mmol/L and 2 HPP > 11.1 mmol/L, with or without history of diabetes, were classified as having diabetes mellitus. Blood pressure measurement was done using a mercury sphygmomanometer. Systemic hypertension was considered in patients with two consecutive systemic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 85 mmHg  .
A history of significant alcohol intake was defined, based on recommendations from NHS Scotland, as ingestion of more than 21 units of alcohol per week for men and more than 14 units per week for women  . A positive history of smoking was defined as having smoked 1 pack-year or more for five years. One pack-year means smoking 20 cigarettes a day, every day for 1 year  .
Self-reported history of hearing loss was also documented. However, types of hearing loss were not distinguished.
These steps were followed by a careful anterior segment slit lamp examination for pseudoexfoliative material on anterior segment structures. Gonioscopy was done using a three-mirror gonio lens to determine open or closed angle of the anterior chamber, presence of dandruff-like materials in the trabecular meshwork, and assessment of Sampaolesi’s line and trabecular pigmentation.
2.7. Definition of Terms
The following terminologies and classifications were used in the study.
Pseudoexfoliation syndrome (PXS): This was defined by the presence of pseudoexfoliative material (PXM) at the pupil border on undilated examination, or anterior lens capsule on dilated examination, or by the trabecular meshwork on gonioscopy, with or without Sampaolesi’s line and pigment deposition in the angle  .
Pseudoexfoliation glaucoma (PXG): This was defined by the presence of glaucoma as defined above with PXS  .
Pupil dilation: A good pupil dilation was noted when pupil size was > 5 mm at least 30 minutes following the application of a short-acting mydriatic agent, and poor if pupil size was 5 mm or less.
Severity of glaucoma: This was determined by the cup-disc ratio (CDR) and CVF. CDR of 0.5 - 0.6 was considered mild damage, 0.6 - 0.8 was considered moderate damage, and greater than 0.8 was considered severe damage.
The severity of glaucoma was classified based on the gray scale and mean deviation using the Hodapp- Parrish-Anderson criteria for staging glaucoma  . Accordingly in the grey scale, no visual field changes are taken as normal, generalized depression/Siedel scotoma as mild defect, semi-arcuate-bi-arcuate/ring scotoma as moderate defect and tunnel-complete loss as severe defect. On the mean deviation, −0.01 to −6.00 dB is regarded as early defect, −6.01 to −12.00 dB as moderate defects, −12.01 to −20.00 dB as advanced defect and >−20 dB or worse as severe defect.
2.8. Data Analysis
Data were analyzed using the Statistical Package for Social Sciences (SPSS), version 16 (SPSS Inc), and reported as frequency distributions, percentages and means ± standard deviation (SD). Statistical testing for significance of observed intergroup differences were performed using the chi-square test for categorical variables and Student’s t-test for continuous variables. In all comparisons, P < 0.05 was considered to be statistically significant (confidence level = 95%).
One hundred and forty adult glaucoma patients were recruited for the study. The age range was between 40 and 89 years with mean age of 60.5 ± 11.9 SD. There were 93 (66.4%) males and 47 (33.6) females (M:F, 2:1). Patients were predominantly Yorubas 76 (54.3%). Sociodemographic information is shown in Table 1.
Thirty four patients (24.2%) reported a significant history of alcohol intake, and 7 (5%) were regular smokers. The social and medical history of the study patients is presented in Table 2.
The age-adjusted prevalence rate of PXG among newly diagnosed POAG patients was 16.9% as calculated by indirect standardization. PXM was seen on the pupil (39%), on the iris (34%), anterior capsule (20%), anterior chamber (5%), and on the corneal endothelium (2%).
The ages of PXG patients were between 45 and 82 years with mean age of 60.8 ± 9.3 years and modal age of 50 - 59. A higher proportion of PXG patients were males compared to females, with a ratio of 1.6:1.
Out of the 25 patients with PXG, 19 (76%) were found to have bilateral PXG and the remaining 6 (24%) had unilateral PXG, four in the right eye and two in the left eye.
Ocular features seen among the PXG patients are shown in Table 3. Pupil size was found to be 5 mm or less 30 minutes after application of topical tropicamide in 44% of PXG patients (OR 0.615, P = 0.0001, CI 0.454 - 0.834).
A higher proportion of PXG patients, 20; 80%), had cataracts when compared with the POAG group, 72 (69.2%) (χ2 = 0.612, OR = 2.34, P = 0.367, CI = 0.81 - 6.75).
The vertical cup-disc ratio was compared in PXG and POAG patients, as shown in Table 4. The missing data were unable to be obtained from patients whose fundi could not be viewed.
There was no statistically significant difference between the mean IOP values of patients with PXG and POAG in either eye (PXG vs POAG: right eye 18.7 ± 8.0, left eye 20.0 ± 10.2, P = 0.875 vs right eye 19.1 ± 9.6, left eye 18.5 ± 0.443, P = 0.443).
The extent of visual field damage in PXG patients was found to be severe compared to POAG patients, and
Table 1. Socio-demographic distribution of study patients.
Table 2. Social and medical history of the study patients.
this was in tandem with the optic disc damage (PXG vs POAG: 47.8% vs 21.3%, P = 0.015).
Patients aged between 50 and 59 accounted for most of the PXG 8 (32%) and POAG 28 (26.8%) cases. Table 5 shows the age distributions of PXG and POAG patients. A higher proportion of males accounted for onset of PXG 15 (60%) and POAG 71 (68.3%) though not statistically significant, Table 6.
Table 3. Ocular features peculiar to PXG eyes among study patients.
Table 4. Optic disc damage in PXG and POAG patients.
Table 5. Age distribution of PXG and POAG patients.
χ2 = 45.841, df = 1, P = 0.0001.
Table 6. Effect of gender on the onset of PXG.
Chi square test = 1.715 Odd Ratio = 0.783, 95% CI of OR (0.33 - 1.84). Key * Only 129 patients among the total 140 patients were compared that is 25 patients with PXG and 104 patients with POAG. The other patients were excluded from the comparison.
Patients a with positive history of cigarette smoking were significantly more common in the PXG group 5 (17%) (P = 0.002, OR 21.04, CI 2.23 - 188.52).
A higher proportion of patients in the PXG group, 15 (60%), were found to have systemic hypertension, as compared with the POAG group (46.1%). For diabetes mellitus, the proportions of patients with the condition in the PXG and POAG groups were 24% and 17%, respectively. However, these differences were not statistically significant (P = 0.187 for systemic hypertension; P = 0.291 for diabetes mellitus).
The mean age of the glaucoma patients in this study was similar to the mean age of 58.13 ± 13.8 observed in a similar study of Nigerian patients by Olawoye et al.  , and 67.4 ± 2 observed in a South African study by Mdlankomo  . The modal age of the patients was in the 50 - 59 years age group for both PXG and POAG. This is reflective of the age specific study population of these studies.
There were more men than women with PXG in this study. This is similar to findings in surveys by Olawoye et al. and Mdlankomo   . This may be accounted for by the larger proportion of male participants in the surveys. There was a predominance of the Yoruba tribe in the study population, and this was similar to findings in the study by Olawoye et al.  . This study was carried out in the southwestern part of Nigeria, which is predominantly populated by the Yoruba ethnic group.
The prevalence rate of PXG among glaucoma patients in this study was in agreement with studies by Stephen et al.  and Rotchford et al.  , which found the prevalence of PXG among glaucoma patients to be 16.4% and 25%, respectively. Olawoye et al. and Thomas et al. found much lower PXG prevalence, 3.5% and 4.2% respectively   . This disparity may have been due to the larger sample size used in these studies.
The laterality of PXG observed in this study was similar to the findings by Yeshigeta et al.  , which noted a bilateral occurrence of 66.7% and unilateral occurrence of 33.7%. This observation also concurred with other similar studies  -  . This is expected since the disease process is usually bilateral, as elucidated by Prince et al.  .
Pseudoexfoliative materials (PXM) were predominantly seen on the pupil, anterior iris and anterior lens capsule in decreasing frequency in PXG patients. The finding of 39% of PXM on the pupillary margin was in conformity with studies by Ghosh et al. that documented pseudoexfoliates to be found on the pupillary margin in 32% - 94% of PXS cases  .
Poor pupillary dilation was observed in PXG patients and was clinically significant (P = 0.0001). This was in agreement with other studies showing eyes with PXS to have significantly more poorly dilating pupils compared to those with POAG and diabetes   . This is as a result of infiltration of iris stroma with excessive extracellular matrix, causing mechanical obstruction of the dilator muscles during mydriasis  . Furthermore, histological studies have shown the presence of fibrotic disorganized or degenerative muscle tissue in most PXS and PXG specimens and not in controls   . Poor dilation also may be partly due to subclinical posterior synechiae from the PXM forming an apposition to the posterior iris.
There was no statistically significant difference in IOP between the PXG and POAG groups. Although in a few cases PXG patients had higher IOP, these findings may be due to chance. This finding was in contrast to previously published results, in which PXG patients have shown higher IOPs than POAG patients   . The reason for this difference may be due to a relatively smaller sample population used in this study, or perhaps in our environment, IOP in PXG patients may be similar to that in POAG patients. However, Olawoye et al. in their study in a Nigerian environment noted a higher IOP amongst patients with PXS than in those without  . Hence, further studies on the IOP comparison between these two groups of glaucoma patients are necessary in Nigeria to establish the pattern of differences in IOP between these groups of patients.
A higher proportion of optic disc cupping was observed among PXG patients in comparison to POAG patients, and this was clinically significant (P = 0.019). This finding agrees with other studies confirming that glaucoma in PXS has a more serious clinical course and worse prognosis than POAG   . Another study showed eyes with unilateral PXS having unilateral optic disc changes in the eyes with PXS, even though equal IOP was observed in both eyes of the pairs  . This suggests that the exfoliative process itself may be a risk factor for optic disc changes.
Visual field damage seen in PXG patients was found to be more severe than in POAG patients and this was clinically significant (P = 0.014 in the right eye and P = 0.025 in the left eye). This is also in agreement with the other studies that show PXG patients to have a significantly higher frequency and severity of visual field damage than POAG patients   . The implication for practice is that eye care providers will need to search for this subtype of glaucoma while evaluating glaucoma patients in order to institute appropriate treatment to combat the more aggressive nature of this disease.
In this study, there was a statistically significant relationship (P = 0.0005) between hearing loss and PXG. Shazly et al. noted a clinically significant hearing loss in 8.1% of PXS patients  . The comparatively high frequency noted in this study may be due to differences in the study populations. In addition, history of hearing loss in this study was self-reported. No objective evaluation of hearing loss was done. Shazly et al’s survey was among PXS and not PXG patients. Cahill et al. reported that a large proportion of patients with PXS have sensorineural hearing loss in comparison to age matched controls, regardless of whether or not there is associated glaucoma  . Furthermore, Turgut et al. in a recent study reported a high prevalence of asymptomatic vestibular dysfunction among patients with PXS  .
Previous studies have shown PXS and PXG to be associated with increasing age   . This pattern was not seen in this study, which found no significant difference in the ages of patients with PXG vs POAG. Other possible risk factors that were assessed in this study included gender, effect of alcohol, systemic hypertension and type 2 diabetes mellitus, all of which showed higher proportions in PXG patients but these findings were not statistically significant.
Limitations of the Study
Extrapolation of findings from this study is limited by its hospital-based nature. The inter-observer variations of cup-disc ratio are also a limitation of findings in this study. In addition, the diagnosis of pseudoexfoliation glaucoma was strictly on clinical evaluation without a polymerase chain reaction to identify the lysyl-oxidase-like-1 (LOXL1) gene. This method has the potential to result in false positives, exaggerating the estimated prevalence. Hearing loss was only self-reported and there was no objective measurement of the type of hearing loss carried out in the study. This could have misrepresented its frequency in the PXG population.
The prevalence of pseudoexfoliation glaucoma is relatively higher than what was previously reported among glaucoma patients within our environment. Significant association with PXG was found for poor pupillary dilatation, severe clinical course and hearing loss. A population-based study is suggested to further define the prevalence and characteristics of PXG and PXS in this region. Eye care practitioners should make a careful search for this subtype of open angle glaucoma because of its more severe clinical course, in order to enhance effective treatment and prevention of blindness.
Conflict of Interests
None of the authors have any proprietary interests or conflicts of interest related to this submission.
This submission has not been published anywhere previously and it is not simultaneously being considered for any other publication.
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