Characteristics of 244 patients with keratoconus seen in an optometric contact lens practice

Authors


Abstract

Background

The purpose of this study was to describe the characteristics of keratoconic patients seen in a specialised contact lens practice from a general population with a high prevalence of the disease.

Methods

Patients attending a contact lens practice for management of keratoconus were asked to complete a questionnaire. Data were collected on demographic characteristics, general health, family history, eye rubbing, allergy, asthma, eczema, education level, history of keratoplasty and smoking.

Results

Two hundred and forty-four patients completed the questionnaire. There was a male bias (54.5 per cent). The majority of the patients (78.7 per cent) wore contact lenses, of whom 67.7 per cent wore hard, 13 per cent soft and 4.2 per cent scleral contact lenses. Some of the patients (21.3 per cent) had undergone corneal graft surgery. Eighteen per cent had an associated systemic disease, the most common of which was type 2 diabetes, although this disease was less prevalent, but not significantly, in the keratoconic sample than in the general population (p = 0.19). The prevalence of eye rubbing (65.6 per cent) was similar to other studies. Compared to the general population, asthma (13.2 per cent) was slightly, but not significantly, less prevalent (p = 0.17), eczema (6.6 per cent) was significantly less (p < 0.001) and allergy (34.4 per cent) was more prevalent (p < 0.001). A high proportion of patients reported a family history of the disease (27.9 per cent) and most were better educated than the general population.

Conclusion

The results of this survey concur with those of other studies with regard to most known characteristics of keratoconus; however, the proportion of asthma and eczema tended to be less than in other surveys and may be linked to the environmental influence of a hot and sunny country. The high prevalence of positive family history of the disease in this cohort suggests a genetic influence.

Keratoconus is a condition in which the cornea assumes a conical shape because of thinning and protrusion.[1, 2] The disease has its usual onset at puberty and in many cases progresses until the third to fourth decades of life, when it usually arrests.[1, 3, 4] In the early stages of the disease the patient may be asymptomatic but as it progresses the main symptom is a mild to severe visual impairment due to irregular astigmatism, myopia and frequently corneal scarring. The main early biomicroscopic signs of the disease are a Fleischer's ring, which is a partial or complete circle iron deposition in the epithelium surrounding the base of the cone, Vogt's striae, which are fine vertical lines produced by compression of Desçemet's membrane and corneal scarring. The predominant optical aberration of a keratoconic eye is coma[5-9] and the cone becomes less touch-sensitive.[10] The condition is associated with a multitude of diseases,[2] such as Down syndrome, Ehlers-Danlos syndrome, Leber's congenital amaurosis, osteogenesis imperfecta and connective tissue disorders.

Management of early cases of the disease is usually achieved with spectacles. As the disease progresses and the astigmatism worsens, specialised types of rigid contact lenses become the principal therapeutic method.[11-18] In advanced to severe cases and when the patient has become intolerant to contact lenses and/or good vision cannot be attained with contact lenses, keratoplasty is performed. About 10 to 25 per cent of keratoconic patients are managed surgically.[4, 13-15, 18-20] Lately, intrastromal corneal ring segments[16, 21] and collagen cross-linking therapy[22] have become surgical options in the treatment of keratoconus and can be combined with contact lenses.

The aetiology of the disease is still unclear, although genetic[23-26] and environmental factors[16, 27] influence the development of keratoconus. The cause is clearly multi-factorial. A commonly accepted view is that the disease may be triggered by environmental factors in genetically susceptible individuals.[23, 25, 28] A strong indication of genetic influence comes from a positive family history of keratoconus in patients afflicted by the disease. Reports vary from 3.34 per cent[26] in first-degree relatives to 23.5 per cent in close and distant relatives.[20] Moreover, in the last few years it has been reported that the prevalence of the disease varies among ethnic groups,[20, 29-32] which may reflect genetic or geographical influences.

Atopy is thought to be associated with keratoconus;[4, 14, 18, 33-38] however, there are conflicting reports on its effect[39, 40] and several authors did not find a statistically significant difference between subjects with keratoconus and a control group.[34, 41-43] Yet, Kaya and collegaues[36] showed that individuals with keratoconus and atopy had a steeper and thinner ectatic area than individuals with keratoconus but without atopy.

There seems to be strong evidence of an association between keratoconus and eye rubbing. The effect has been demonstrated in several case-controlled studies[25, 41, 44, 45] and confirmed in a meta-analysis.[28] There seems to be some evidence supporting the role played by ultraviolet radiation, as a high prevalence of the disease has been reported in hot, sunny countries, such as Saudi Arabia,[46] India[47] and Israel.[30]

Several retrospective reports of the profile of keratoconic patients have been conducted in different locations around the world. Most of these have been aimed at evaluating the demographic profile and management of the disease,[12, 13, 15, 20, 48] others at assessing its progression,[4, 45] while yet others were aimed at detecting the main associated factors.[20, 45] In their large study, Owens and Gamble[20] designed a questionnaire, which was self-administered by keratoconic patients across New Zealand. A total of 673 questionnaires were completed. It was found that there was a male predominance (58.5 per cent) and that the disease was significantly associated with allergy and eye rubbing, as well as a family history of keratoconus. The aim of the present study was modelled on that conducted by Owens and Gamble,[20] that is, to evaluate the characteristics associated with keratoconus in Israel, where the prevalence of the disease has been shown to be high.[30]

Methods

Data were collected from keratoconic patients who attended a specialised private contact lens practice in Tel Aviv, Israel. The vast majority of the patients attending this clinic had keratoconus. All patients had been previously diagnosed with keratoconus in at least one eye by an ophthalmologist and referred to this clinic for contact lens management rather than surgery. Patients came from all parts of the country. We used a questionnaire, which had been tested before[30] and was based on one used in another study of keratoconus.[20] It was designed to assess the demographics and other features in established keratoconic patients. All the patients with keratoconus, who attended the practice between September 2009 and May 2011, were given the questionnaire, which they were asked to complete. The questionnaire consisted of mostly single-response questions and a few multiple-response questions. The following data were collected: gender, ethnicity, family history of keratoconus, general health, eye rubbing, allergy, asthma, eczema, education level, history of corneal graft surgery and smoking. To assess eye rubbing the questionnaire asked the patient to estimate the frequency of the rubbing on a scale of 1 (not at all) to 5 (almost constantly).

The nature of the study was explained to all the patients before signing an informed consent form. The study followed the tenets of the Declaration of Helsinki and was approved by Hadassah College ethics committee. Data were analysed as mean, standard deviation (SD) and 95 per cent confidence intervals (CI). The chi-square test for categorical variables was performed to investigate the presence of an association between allergy, asthma, eczema, diabetes and keratoconus. A p-value of less than 0.05 was considered significant.

Results

Of the approximately 290 patients with keratoconus who had been given a questionnaire, 244 completed it (84 per cent). The mean age of the keratoconic subjects was 38.6 ± 11.5 years, with a male gender bias of 54.5 per cent (95 per cent CI: 48.25–60.74). The majority of patients (78.7 per cent [95 per cent CI: 73.6–83.8]) wore contact lenses. Half of them alternated between contact lens and spectacles wear. The rest of the patients (n = 52, 21.3 per cent) wore spectacles most of the time. A similar number of patients (52, 21.3 per cent) had undergone corneal graft surgery. Details relating to lens type are given in Table 1 and are compared with the results obtained by Owens and Gamble.[20]

Table 1. Percentage of individuals wearing contact lenses and having undergone penetrating keratoplasty (PKP)
 SoftRigid gas-permeableGas-permeable scleralOtheraPKP
  1. aIncludes piggyback, SoftPerm, one eye with hard and the other with soft
Owens and Gamble[20]7.183 2.520
Current study1367.74.215.121.3

Most subjects with keratoconus defined themselves as either Ashkenazi (48.77 per cent) or Sephardic (45.90 per cent); the remaining sample consisted of Arabs and individuals who did not specify their ethnic origin. The vast majority of the patients referred to this clinic were Jews because Arabs are usually referred to clinics closer to their place of residence, such as Jerusalem and the north of the country.

The keratoconic subjects were significantly more educated than the general population. In the keratoconic cohort, 31.6 per cent had full high school matriculation, 41.4 per cent had a Bachelor's degree and 18.4 per cent a Master's degree or higher compared to 23.1, 14.4 and 8.5 per cent, respectively, for these levels of education in the general population according to the Israel Central Bureau of Statistics (ICBS).[49]

Some of the subjects with keratoconus (18 per cent [95 per cent CI: 23.5–22.5]) had some general health problems. The largest group was diabetes (4.1 per cent, n = 10) of which eight had type 2, followed by hypertension, thyroid abnormalities, multiple sclerosis and high blood cholesterol. The prevalence of diabetes in the general population in Israel was found to be higher, being 6.1 per cent from a report by 1,653 physicians across the country responsible for 1,409,725 adults,[50] although the difference was not significant (p = 0.19). Regarding family history of the disease, 27.9 per cent (95 per cent CI: 22.4–33.6) of the respondents reported at least one person in their family with the disease, of which 50 (20.5 per cent) were first-degree relatives.

Of the subjects with keratoconus, who were 20 years of age and older, 16.4 per cent (95 per cent CI: 11.8–21.04) mentioned smoking regularly. This figure is lower than the ICBS data,[49] which gives 19.4 per cent for the general population of the same age group. Our result is also in agreement with another study, in which smokers formed a significantly smaller percentage of keratoconic patients compared with the average population.[51]

The results for eye rubbing, allergy, asthma and eczema are shown in Figure 1. Eye rubbing was reported by a large number of keratoconic subjects (65.6 per cent [95 per cent CI: 59.6–71.6%]). These data relate to any level of eye rubbing; however, the frequency of rubbing varied among individuals and followed a normal distribution (Figure 2). It showed that the majority reported rubbing their eyes moderately.

Figure 1.

Percentage of eye rubbing, allergy, asthma and eczema for the keratoconic participants of this survey (white bars), for the general population[52] (black bars) and from the survey by Owens and Gamble[20] (grey bars)

Figure 2.

Frequency of eye rubbing distribution in patients with keratoconus on a scale of 1 (not at all) to 5 (almost constantly); n = 160

Allergy was reported by 34.4 per cent (95 per cent CI: 28.4–40.4%) of patients with keratoconus. The percentage in the general population in Israel who reported an allergy was found to be 20 per cent,[52] a significantly lower value than among our keratoconic participants (p < 0.001). The percentage of subjects with keratoconus who reported having asthma was 13.2 per cent (95 per cent CI: 8.7–17.6%), which is similar (p = 0.71) to that reported in the general population in Israel (14 per cent).[52] The percentage of keratoconic subjects who reported having eczema was 6.6 per cent (95 per cent CI: 3.6–9.9%), a value slightly lower than that reported for the general population in Israel (eight per cent),52 although the difference was significant (p < 0.001).

Discussion

In accord with recent studies, there was a preponderance of men over women.[10, 15, 20, 29-31, 41, 45, 53] Papers published earlier report the opposite.[54-56] Interestingly, the difference in the male to female ratio of keratoconus that occurred in a period of 36 years was clearly described in a retrospective study in the Netherlands.[57] For cases diagnosed in the period 1950 to 1954, the ratio of male to female was equal to 0.5 and remained less than 1.0 until 1970, when the number of male patients with the disease strongly increased, while the number of female patients remained virtually unchanged and the ratio reached 1.58 for the patients diagnosed in 1985 and 1986. The reason for this phenomenon is not clear.

The general level of education of the subjects with keratoconus was higher than in the general population. This observation was consistent with the highly educated cohort of the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) study[18] and it may reflect the fact that in both studies the patients were self-selected from private or university contact lens practices.

The results of this survey confirm the role of eye rubbing as an important association and our data are similar to other studies, in which the results ranged from 40 per cent for gentle rubbing[44] to 73 per cent for an abnormal amount of rubbing.[58] Other investigations cite figures in between comprising vigorous and gentle rubbing, although most of these did not specify the level of eye rubbing (Table 2). In a meta-analysis of studies of eye rubbing compared with a control group, the odds ratio (OR) and 95 per cent CI were calculated to be OR: 2.23, CI: 1.87–22.65[28] and it clearly indicated a significant association with keratoconus. The fact that a large percentage of patients with keratoconus do not report any eye rubbing, 46 per cent in the CLEK study[18] and approximately the same percentage in our study, reflects the multifactorial cause of the disease. Thus, eye rubbing is one risk factor, which contributes to the disease and perhaps triggers it in genetically susceptible people.[23, 25]

Table 2. Percentage eye rubbing, allergy, asthma and eczema in keratoconic patients from various studies
StudyYearEye rubbingAllergyAsthmaEczema
  1. A: Asian, W: White
Copeman[60]19656627 32
Karseras and Ruben[58]19767334.634.618.6
Rahi and collegaues[37]1977 1532
Gasset, Hinson and Frias[34]197844–5035.717.98.2
Swann and Waldron[38]1986 42.215.812.3
Ihalainen[53]1986 35824
Harrison and collegaues[35]198964.637.328.431.3
Tuft and collegaues[4]1994 35.225.219.9
Zadnik and collegaues[18]199850.45314.98.4
Owens and Gamble[20]200362573430
McMonnies and Boneham[44]200340–5839  
Georgiou and collegaues[29]2004 20 W, 9 A38 W, 18 A14 W, 7 A
Assiri and collegaues[46]200544.839.25.68
Weed and collegaues[45]200848302314
Nemet and collegaues[59]2010 17.68.2 
Current study201265.634.413.26.6

The reported prevalence of atopic conditions in patients with keratoconus varies widely, especially with regard to asthma and eczema (Table 2). Some authors reported atopy without specifying the conditions for which it is responsible.[13, 14, 39, 41] In one such study, the role of atopy was analysed by logistic regression and it was not found to be significantly different between keratoconic subjects and controls,[41] confirming an earlier study.[43] Our data for asthma are consistent with another study conducted in Israel in which a self-reported prevalence of asthma by patients with keratoconus was also found to be low at 8.2 per cent, although this was significantly higher than in a control group (4.1 per cent).[59] Data from other studies reporting the prevalence of asthma were at least twice as high[4, 20, 35] (Table 2) and only slightly less than in the CLEK study[18] and Swann and Waldron's survey[38] but higher than for the very unusually low figure (three per cent) reported by Rahi and collegaues.[37]

With regard to eczema, the results are equivocal. Many studies report an association with keratoconus without a comparison to a control group.[20, 35, 60] Several studies, including ours, found a low prevalence of eczema in patients with keratoconus, being lower than in controls in some studies,[37, 45] while others found no difference between subjects with keratoconus and controls.[34, 42, 43] Most of the studies presented in Table 2 report results about three times higher than ours, except for the CLEK study, which is similar to ours and the very low figure (two per cent) reported by Rahi and collegaues.[37] It is noteworthy that the data for asthma and eczema reported for individuals living in hot, sunny locations, such as Israel (present study), Saudi Arabia,[46] Australia[38] and Florida[34] are much lower than in most of the other studies. This difference is also found between Caucasians and Asian patients (Bangladesh, India and Pakistan) in the Midlands of England,[29] although we do not know whether the Asian subjects were born in Asia or in England.

Our findings for allergy, most of which was induced by pollen, dust, antibiotics and animal fur, were consistent with the other studies described in Table 2. There seems to be an aggregation of data ranging between 27 and 40 per cent, with two outliers above[18, 20] and two below this range but both of them significantly higher than controls.[37, 59] Our data suggest an association between keratoconus and allergy. Although the itch induced by allergy may cause eye rubbing, it is not the only provocative factor, as a much higher percentage of patients rubbed their eyes than had an allergy.

The most common systemic disease reported by our keratoconic subjects was diabetes, although diabetes and keratoconus have opposite effects. Diabetes stiffens the cornea, whereas only the affected stroma appears to lose tensile strength in keratoconus.[61] Diabetes is considered to be protective by inducing cross-linking of corneal collagen.[22]

Our data of a positive family history of keratoconus were higher than the findings for all other studies, most of which report values less than 20 per cent,[2, 53, 62] except Owens and Gamble's study[20] in New Zealand, in which 23.5 per cent of their keratoconic sample had a positive family history and the study of Millodot and collegaues,[30] in which the figure was 21.7 per cent, but this latter study involved a small sample (n = 23). The high percentage of patients reporting a positive family history may stem from the fact that endogamy is common among the Israeli population. This is similar to the situation noted in northern compared to southern Finland, where the percentage of family history is 19 versus nine per cent[53] and similarly with the large families of Maori/Polynesian populations.[20] In these large families with many children, there is a higher probability of recessive genes to be expressed.[63] A large positive family history of the disease, as found in this study, may stem from either environmental or genetic influence. It is not clear which factor predominates and further research is needed to elucidate this important question.

UV radiation may be related to keratoconus. A large prevalence of the disease has been observed in countries with a lot of sun exposure and dry conditions for most of the year as prevails in Saudi Arabia,[46] India[47] and Israel.[30] Prevalence is much lower in areas with less sun exposure and lower average annual temperatures, such as Finland,[53] Denmark,[64] the Urals,[65] Minnesota,[66] Japan[32] and Macedonia.[67] This may point to the environmental effect of excessive sun exposure of patients with keratoconus in this study. Although to our knowledge there is no investigation of the effect of sun exposure on keratoconus in humans, it is a compelling possibility. Ultraviolet light is a source of oxidative stress and keratoconic corneas have a reduced ability to process reactive oxygen species, thereby resulting in oxidative damage[27, 68] due to reduced levels of antioxidants.[69] This process triggers a cascade of events, such as an alteration of various corneal proteins, increased enzyme activities and apoptotic cell death, which leads to keratoconus.[27] In mice, UV radiation was observed to cause the development of keratoconus.[70] With the observation of a high incidence of acquired chromosomal abnormalities in the human keratocytes, where these cytogenetic abnormalities are absent in childhood and accumulate throughout life,[71] it seems plausible that environmental factors, such as sun (UV) exposure could lead to the development of keratoconus.

Our findings regarding the proportion of patients with keratoconus wearing contact lenses (78.3 per cent) were similar to those of Owens and Gamble[20] (80 per cent) and 74 per cent in both the CLEK[18] and Lass and colleagues studies,[14] although some authors have reported lower figures, such as 53.3 per cent.[13] In our study, the proportion of keratoconic subjects wearing soft lenses was much higher than in the CLEK[18] and Owens and Gamble studies[20] (13 versus 3.5 and 7.1 per cent, respectively). Hence, the number of wearers of rigid gas-permeable lenses was smaller (67.7 per cent) than in either study (92 and 83 per cent, respectively). The other studies report the use of piggyback[20] (7.3 per cent) and SoftPerm[18] (4.8 per cent) contact lenses. Interestingly, the CLEK study[18] did not describe any use of scleral contact lenses and Owens and Gamble[20] gave a figure of 2.5 per cent for other lens types, which may include scleral lenses, although there is no mention of it. In our survey, scleral contact lenses made up 4.2 per cent of the cohort. In our sample, very few patients were corrected with SoftPerm lenses, possibly because of complications, which have been documented.[72]

This study describes various associated features of keratoconus in a large cohort of patients residing in a hot, sunny country with a high prevalence of the disease. There are some limitations, which stem mainly from the reliability of the history reported by patients in a self-administered questionnaire. The results confirmed those of other surveys with regard to contact lens management, albeit with a greater percentage of gas permeable scleral lens therapy and with the percentage of patients who had undergone corneal graft surgery. The proportion of eye rubbing, an environmental factor, was also consistent with other similar surveys. The prevalence of asthma and eczema was low, like data obtained in similarly hot and sunny countries. There was also a higher proportion of positive family history of the disease. This and the association with allergy may be evidence of an underlying genetic influence to the disease.

Acknowledgements

Dr Einat Shneor received a grant from the Israel Society of Psychobiology. Mr Shmuel Behrman and Mr Ilya Ortenberg work are practitioners at the Microlens practice. Mr Behrman has a financial interest in manufacturing contact lenses.

Ancillary