Clinical Profile of Omani Keratoconus Patients: An Experience from a tertiary referral centre in Muscat.

OBJECTIVE: To determine the demographics and associated clinical features of Omani keratoconus patients presenting to the Ministry of Defence Hospital (MODH) in Muscat.
METHODS: This is a retrospective, descriptive study whereby the electronic medical records of all Omani keratoconus patients presenting to the MODH between January 2011 and December 2015 were reviewed. Demographic details, corrected distance visual acuity, refraction, corneal topography, pachymetry, and treatment received were all documented.
RESULTS: There were 458 new keratoconus patients (257 males, 201 females) comprising a total of 893 eyes with a mean age of 20 years ± 5.6 (standard deviation) (range 6-46 years). On their first visit, 35% of eyes had spectacle-corrected distance visual acuity <0.5 logarithm of the minimum angle of resolution (LogMAR), 38% had central corneal thickness <450 um, and 25% had a mean keratometry more than 53 Diopter (D). According to the Amsler-Krumeich classification, 37%, 30%, 18%, and 16% of eyes classified into stages I, II, III, and IV, respectively. The severity of keratoconus did not correlate with the age of patients (rs = -0.13, P < 0.05). Over the 5-year period of the study, 502 eyes were fitted with rigid gas permeable lenses with 91% achieving the vision of 0.1 LogMAR or better, 22% of eyes underwent collagen cross linking, 3% underwent intracorneal ring segments implantation, and 4% underwent corneal grafting.
CONCLUSION: A significant proportion of Omani keratoconus patients seen in the MODH showed advanced disease on their first visit. There was no correlation between severity and age suggesting that keratoconus can progress quickly in our pediatric group. Population-based studies are an important next step. Meanwhile, early detection and timely interventions to limit the burden of the disease are crucial.

Introduction

Keratoconus is a noninflammatory, bilateral disease of the cornea characterized by progressive thinning and apical protrusion.[1] It can lead to severe reduction in vision and may progress to require corneal transplantation at a young age.

Keratoconus is a chronic disease with an age of onset normally in the first or second decades of life, which is also the progressive phase. The condition tends to stabilize by the third or fourth decades of life.[1] Although the disease is not encountered much in clinical practice in those above the age of 60 years,[2] the disease seems to be as prevalent in the population in such age group as expected in a chronic disease.[3]

Keratoconus shows a clear ethnic disparity. It seems that Arabs, Asians, and Indians have a higher prevalence of the disease as compared to those of European descent.[456789] This is probably due to the former ethnicities having a more severe form of the disease and thus presenting to clinical practice. Consanguinity as well as genetic factors were speculated to be potential contributors for this difference.[410] Keratoconus also appears to affect males more than females,[941112] an observation which is not entirely understood but may be related to a mixture of hormonal and environmental differences between the two sexes.[13]

As eluded above, keratoconus seems to be associated with both genetic and environmental risk factors. Many genes have been speculated to be linked to the pathogenesis of keratoconus.[14] First-degree relatives and twins of keratoconus patients have a higher incidence than the general population.[1516] However, the hereditary pattern does not seem to be common and is neither predictable. Multiple ocular and systemic syndromes have been associated with developing keratoconus including Leber's congenital amaurosis,[17] Down's syndrome,[18] and Ehlers–Danlos syndrome.[19] Environmental factors, such as eye rubbing and allergic eye disease, are thought to play a major role in the expression of the disease.[14]

Early in the disease process, keratoconus may not cause significant morbidity and is often missed.[20] However, advanced disease may lead to significant visual disability requiring corneal transplantation. In fact, keratoconus is currently the second most common indication for corneal transplantation worldwide; Fuchs corneal endothelial dystrophy being the top.[21] The survival rate of corneal transplants for keratoconus was reported to be only 49% at 20 years[22], and thus, many patients may require several corneal transplants during their lifetime.

In Oman, there is a paucity of statistical data on the epidemiology of keratoconus. Recently, Dr. Farrag et al.[23] presented a case series on the risk factors for keratoconus at Al Nahdha hospital during a 15-month period. The authors noted that 22% of cases reported a family history of keratoconus and 39% reported eye rubbing. The mean age of the cohort was 21 years. Nevertheless, clinical characteristics of keratoconus in the Omani population and epidemiological data are still to be explored.

The purpose of this study was to find the clinical profile of Omani keratoconus patients presenting to the Ministry of Defence Hospital (MODH) in Muscat.

Methods

Ethics approval for this study was obtained from the MODH Research and Ethics Committee, and this study was carried out according to the guidelines of the Declaration of Helsinki.

The MODH is a military tertiary referral center for ophthalmology in Oman and receives referrals from all over the country. Eligible people include military personal and their first-degree family members. However, the hospital does receive a large number of patients which do not fit the above criteria who require specialized care not available elsewhere in the country.

The electronic medical records of all Omani keratoconus patients presenting for the first time to the MODH between January 1, 2011 and December 31, 2015 were reviewed.

Demographic details, autorefraction (ARK-1, Nidek, Japan), corrected distance visual acuity (measured using Snellen chart and converted into logarithm of the minimum angle of resolution [LogMAR]), corneal topography (OPD scan ARK-10000, Nidek, Japan), central corneal thickness (Pachette 2, DGH Technology, USA), and treatment received were documented. Data on slit-lamp signs of keratoconus were not uniformly documented, and therefore, were not included in the study to avoid bias. A clinical diagnosis of keratoconus was performed based on a combination of clinical signs including, frequent change in refractive error, scissoring on retinoscopy, suspicious placido disc-based anterior curvature map (e.g., asymmetrical bowtie with skewed radial axis), corneal thinning, and slit-lamp signs of keratoconus. Eyes previously treated elsewhere with cross linking, intracorneal rings, and corneal transplantation were excluded from the clinical characteristics analysis.

Amsler-Krumeich classification was used to classify the keratoconic eyes. A single criterion was used for inclusion in a particular stage (whichever is more severe).[24]

The present study used mean keratometry (mean K) of the central 3-mm zone when obtained from autorefractors or simulated keratometry (simK) when obtained from topography maps as a measure of the severity of keratoconus. Studies have shown that mean K and simK are similar.[25] However, in advanced cases of keratoconus, the topography machines often do not produce accurate images of the anterior corneal curvature, and SimK values may be missing. In this regard, the study used the autorefractor's mean K values for the Amsler-Krumeich classification and the correlation analysis.

The mean K was found to be nonnormally distributed using Kolmogorov–Smirnov test. Therefore, the Mann–Whitney test was used to assess the difference in severity of keratoconus between genders and spearman correlation coefficient was used to evaluate the strength of the linear relationship between mean K and age. All tests were two-tailed and P < 0.05 was considered statistically significant.

Data were analyzed using the Statistical Package for Social Sciences version 21 (IBM, NY, USA).

Results

There were 458 new keratoconus patients (257 males and 201 females) comprising a total of 893 eyes [Table 1]. The mean age of all patients was 20 years ± 5.6 standard deviation (SD) (range 6–46 years).

Table 1

Demographics

Fifty-nine eyes were previously treated elsewhere with cross linking, corneal rings, or keratoplasty and were excluded from further analysis. Eight eyes had missing vision and refraction values, 29 eyes had missing mean K values, and 34 eyes had missing pachymetry values.

On their first visit to MODH, the mean spectacle-corrected distance visual acuity (SCDVA) of the eyes was 0.4 LogMAR (range 0.0–1.50, SD = 0.4) with 35% being worse than 0.5 [Table 2]. The mean central corneal thickness was 460 um (range 248–652, SD = 45) and 38% of eyes measured <450 um. The median mean K was 49 D (interquartile range [IQR] = 46–53), and median Kmaxwas 52 D (IQR = 48–56). Using the Amsler-Krumeich classification, 37%, 30%, 18%, and 16% of eyes classified into Stages I, II, III, and IV, respectively [Table 3].

Table 2

The spectacle-corrected distance visual acuity (in logarithm of the minimum angle of resolution), pachymetry (in um), and the average (mean K) and maximum (Kmax) refractive power of the anterior corneal curvature (in D) of keratoconic eyes

Table 3

Amsler-Krumeich classification of the keratoconic eyes

The mean K values were 48.4 and 48.7 D for males and females, respectively. Age did not correlate with the severity of keratoconus [Spearman correlation coefficients −0.13, P < 0.05; Figure 1].

Figure 1

A scatter plot showing correlation of Mean K with age (Spearman correlation coefficient = − 0.13,P < 0.05)

In the study period, corneal cross-linking was performed in 183 eyes, 26 eyes were fitted with corneal rings, and 32 eyes had corneal transplantation. Rigid gas permeable (RGP) contact lenses were fitted for 502 eyes and 91% achieving visual acuity of 0.1 LogMAR or better.

Discussion

This study found that the majority of keratoconus patients seen in MODH were young with a mean age of 20 years and a significant proportion having advanced disease with more than one-third of eyes classifying to Stages III and IV according to the Amsler-Krumeich classification. Age at the presentation did not correlate with severity suggesting that keratoconus can progress quickly in children to reach similar severity to that seen in adults.

Other studies in the Middle East with Arab ethnicities found a similar pattern in the age distribution of keratoconus patients with a mean age in the 20s including Saudi Arabia[7] and Israel.[26] However, a higher mean age (>30s) is seen in those of European descent.[272829] In addition to Arab ethnicity, Asians (mostly of Pakistani origin) living in the UK,[10] and Maori and Pacific Islanders in New Zealand seem to present with keratoconus at a much earlier age as compared to Caucasians.[30] This may suggest that some ethnicities are prone to a more severe form of the disease.[431] The variation in the expressivity of the disease is also seen in between family members of what seems to be autosomal dominant keratoconus.[3132] The ethnic variations seen in keratoconus may be influenced by genetic and environmental factors and still remains elusive.

Keratoconus is a bilateral disease, although may be asymmetrical on presentation.[2733] The majority of the patients reported in this study had bilateral disease. The patients with unilateral keratoconus probably had subclinical disease which may manifest with time. If tomography was used, subtle changes may have been identified given the higher sensitivity.[34]

Severe keratoconus seen in many patients in this study is also common in other parts of the world. The collaborative longitudinal evaluation of keratoconus (CLEK) study[35] was a multicenter longitudinal study in the USA with 1209 participants. Almost half of the patients had steep K values of more than 52 D. A study from New Zealand[36] found that more than 50% of patients presented with a median Kmax value of more than 52 D. The Dundee University Scottish Keratoconus (DUSK) study[12] found that the mean value for the simK in their participants was 52 D, and the average corneal thickness was 443 um on presentation. A study from Saudi Arabia found that 18% of cases presented with mean K value of more than 54 D.[7] Unfortunately, the absence of a global consensus on the classification of the severity of keratoconus[37] deters optimal comparability between international data as seen in the later-mentioned studies. Nevertheless, presentation with advanced disease seems to be a common observation.

Regarding visual acuity, spectacles can be adequate in the mild form of the disease. However, RGP contact lenses may be needed in advanced cases without significant corneal scarring.[38] Although more than one-third of our patients had best spectacle-corrected visual acuity worse than 0.5 LogMAR, RGP contact lenses corrected vision to 0.1 LogMAR or better in more than 90% of eyes. This finding was consistent with the CLEK study.[27] Both the CLEK[27] and DUSK[12] had higher rates of corneal transplantation of 10% or more. Only 4% of our eyes had corneal transplantation. Even after including the cases, which have been treated elsewhere the proportion was only 5.4%. The difference may be accounted for by the recent advancements in the management of keratoconus including the use of intracorneal rings, the availability of more comfortable RGP contact lenses, the follow-up periods, and the availability of corneal tissue for transplantation.

Correlation analysis in this study found that age did not correlate with more severe keratoconus using mean K as the severity index. A study from Turkey including 251 patients similarly failed to find any correlation between age and severity of keratoconus including mean K values, pachymetry, and refraction.[11] On the contrary, Léoni-Mesplié et al.[39] studied 216 keratoconus patients including 49 children (≤15 years). The authors found that 28% of children had Stage IV disease (using the Amsler-Krumeich classification) as compared to only 8% of adults. Further analysis of our study results revealed that Stage IV disease was observed in 23% of eyes in children (48 eyes of 180 in total) and only 14% in adults (89 eyes of 643 in total). It is also suggested that keratoconus in children progress faster than adults,[40] and younger age at diagnosis is a predictor of subsequent corneal scarring[41] and corneal transplantation.[42] Severe disease at presentation in children may be explained by the better tolerability of reduced visual acuity at an early keratoconus stages, failing to express their symptoms to their parents, or due to the aggressive nature of the disease. Further research is needed in this area.

The present study is limited by its retrospective nature. Reasons for missing data encountered in the study includes incomplete documentation, technical failure of machines, and unrecordable values due to advanced disease and patients' cooperation or refusal to undergo all investigations. However, missing data were <5% and are unlikely to bias the overall results. In addition, the study did not collect slit-lamp signs because they were not uniformly documented and may bias the results if reported.

Keratoconus is a disease which affects adolescents and young adults, a time where the visual demand is very high for education and early career. The impact on the quality of life is significant.[2743] This is the first study to our knowledge to characterize the clinical features of Omani keratoconus patients. The future studies need to address the epidemiology of the disease in the whole population and inform the necessity for preventative measures.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.