Vision related quality of life among Nepalese patients with keratoconus

Introduction: Keratoconus (KC) is a bilateral progressive noninflammatory disorder characterized by irregular astigmatism and corneal thinning. KC results in a disproportionate impact on major aspects of quality of life (QoL) of a person due to its early onset and chronic nature. This study aims to evaluate vision-related QoL in Nepalese patients with KC. Method: A cross-sectional hospital-based study was carried out for 1 year. A sample of 35 KC subjects and 38 control subjects who met the eligibility criteria were enrolled. All subjects underwent corneal topography and abberometry along with a comprehensive eye examination. Both cases and controls completed the NEI VFQ 25 questionnaire. Visual acuity (high contrast visual acuity and LCVA), CS, color vision, refraction, and scores of all subscales of QoL were measured. The QoL scores were correlated with each of the visual function parameters in KC subjects. Result: The mean scores of all of the subscales of QoL were found significantly less in the KC group than in age and sex matched control group with P<0.001 The mean composite score was found to reduce significantly as the grade of KC increased. The mean composite score for grade 1 KC was 70.79±7.96, grade 2 KC was 60.56±6.49 and for grade 3 KC was 55.99±0.67 with P=0.001 about better eye. There was a highly significant difference in the mean composite score of QoL between these contact lens wearers and spectacle wearers. The mean composite score for spectacle wearer was 67.86±07.99 and that of contact lens wearer was 58.63±04.26 with P=0.004. Conclusion: This study concluded that the QoL of keratoconic individuals was found to reduce gradually as the severity of the disease increased. QoL score in contact lens-wearing Nepalese KC patients is worse than spectacle wearers. By stopping the progression of disease we can maintain functional vision as well as a vision-related QoL. Our study findings suggested that vision and visual function parameters in the better eye is the most important parameter affecting VR-QOL of patients with KC. KC patients should maintain the best vision that they can have.


Introduction
Keratoconus (KC) is a bilateral progressive noninflammatory corneal disorder characterized by anterior corneal protrusion and thinning of the central stroma [1] .It has clinical features like the central corneal thinning and protruding ahead in a cone-shaped fashion resulting in irregular myopic astigmatism, and sooner or later visible impairment [2] .The prevalence in studies can range from 0.3 per 100 000 in Russia to 2300 per 100 000 in Central India (0.0003-2.3%) [3] .KC affects both sexes, even though it is uncertain whether vast variations between males and females exist [3] .KC has its onset at puberty and is progressive till the third to fourth decade of life, while it usually arrests [1] .While early in the disease, there may be no symptoms at all apart from a slight blurring of vision.Clinical signs also differ depending on the severity of the disease progression.With the advancement in technology and a better understanding of the disease, various corneal topographic and biomechanical methods have proved to be of utmost importance in the early diagnosis and suitable classification of KC [4] .Classification based on morphology, disease evolution, ocular signs, and index-based systems of KC have

HIGHLIGHTS
• Quality of life (QoL) can be monitored to evaluate the impact of disease on physical, social, and psychological aspects in the life of a person.• The QoL of an individual was found to reduce gradually as the severity of disease increased and by stopping the progression of the disease.• Contact lens using Nepalese subjects has poor QoL compared to spectacle wearing Nepalese subjects.also been proposed.The Amsler-Krumeich classification is more practical and widely used for KC staging, which utilizes the mean K-value in the anterior sagittal curvature map, the refraction error of the patient, the thickness of the thinnest corneal area, and whether there is scar tissue in the cornea for staging.Clinically objective measures of vision, such as visual acuity, contrast sensitivity, and color vision, are the traditional indicators used in the clinic.
Measuring quality of life (QoL) impact is particularly important in KC because it has an early onset, is progressive and chronic, is associated with frequent changes in refractive prescription, can cause serious vision impairment, and typically requires treatment.KC is a unique chronic eye condition having an early onset in life with a median age of 25 years [5] .Thus, KC is a disease condition with an extremely long duration affecting people during their prime earning, financial growth and career developing ages.With notably impaired vision-related QoL and the particularly young onset of disease, the financial burden of the remedy of KC also represents and draws a large public health concern and is a major factor to reduce the QoL of the person [6] .ʻNational Eye Institute-Visual Function Questionnaire-25(NEI-VFQ-25) is a set of self-administered questionnaires created by RAND with funding from the national eye institute to create a survey that would measure the dimensions of self-reported vision targeted health status of a person with chronic eye diseases like Glaucoma, Diabetic Retinopathy, etc. [7] .NEI-VFQ 25 is a legitimate and relevant predictor of changes in Vision Related Quality of life (VR-QoL) over time either with change in severity of disease or changes/modifications seen after treatment interventions.It has been deemed acceptable in various languages like French, English, Turkish, Italian, Japanese, and Nepalese.The Nepalese version of NEI-VFQ 25 was designed and validated by Dr Rajendra Gyawali which we will use in our study.
This study aims at accessing visual status and vision-related QoL among Nepalese patients with KC.QoL is a subjective measure of the physical, social, mental, and economic well-being of an individual.Similarly, KC being a chronic disease affecting young individuals at their productive age, will create a huge impact on daily living, future plans, and treatment creating an economic burden.This study has tried to determine the QoL in Nepalese subjects with KC.This study tried to compare the QoL scores with healthy emmetropes.Also, this study has tried to pick up the best treatment modality which would significantly improve vision and vision-related QoL.

Materials and methods
It was a hospital based, descriptive, cross-sectional study focusing on patients diagnosed with KC.It was conducted to examine visual status and vision-related QoL in Nepalese patients with KC.Patients diagnosed with KC in the General OPD unit, Cornea, and EOD unit of BPKLOS were recruited in the study, and were carried out for 1 year.Subjects diagnosed as KC at any stage with age between 15 and 50 years and best corrected visual acuity 6/6 to 1/60 were included in the study.KC associated with syndromes like down syndromes, RP, VKC were excluded because they might impact the QoL score and act as confounding.Patients with a history of keratoplasty and associated other ocular pathologies and patients not willing to participate in the study were excluded.Following clinical features were considered for the diagnosis of KC Munson's sign, Rizzuti phenomenon, stromal thinning, posterior stress lines (Vogt's striae), iron ring (Fleischer ring), scarring (epithelial or subepithelial), scissoring on retinoscopy, oil droplet sign.In topography following signs were considered that includes localized increased surface power, inferior superior dioptric asymmetry, and relative skewing of the steepest radial axes above and below the horizontal meridian.Frequent changes in spectacle power and blurred vision were the symptoms that were commonly considered.Informed written consent was taken from all participants in accordance with the WMA Declaration of Helsinki, 1964 after an explanation of the nature of the study.Ethical approval was obtained from the institutional review board of the Institute of Medicine All together 73 subjects were included in the study 35 KC subjects and 38 control subjects (healthy age and sex-matched emmetropes).Among 35 KC, 25 were spectacle wearers and 10 were rigid gas permeable (RGP) contact lens wearers.The diagnosis of KC was done based on clinical signs and symptoms.The other tools employed for the eye examination were slit lamp, log MAR visual acuity chart to determine high contrast visual acuity (HCVA), Peli Robson contrast sensitivity chart to assess contrast sensitivity, Autorefractor (shin-nippon), trial frame, and trial lenses to determine the objective and subjective refraction of patients and Bon Sirius corneal topography machine to obtain corneal topographic and aberrometric analysis.
All the subjects (control and cases) were interviewed using a validated Nepalese version National Eye Institute -Visual Functioning Questionnaire (NEI-VFQ-25) 2000 designed and validated Dr Rajendra Gyawali to measure vision-related QoL.NEI-VFQ-25 is composed of 12 subscales as general health, general vision, ocular pain, near vision, distance vision, visionspecific social functioning, vision-specific mental health, visionspecific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision.The final scoring was based on the scoring manual.Still, there are some controversies regarding the selection of appropriate questionnaires for QoL measurement [7] .Research registry UIN is researchregistry9368 https://www.researchregistry.com/browse-the-registry#home/.The KC subjects were further classified into four groups as per four stages of KC namely stage 1, stage 2, stage 3, and stage 4 according to the Amsler-Krumeich classification.And all the age-sex-matched normal participants were placed in a separate control group.Furthermore, the KC group was also divided into spectacle group and contact lens group also based on the duration of KC diagnosis, that is, greater than 5 years and less than or equal to 5 years.And all the recordings were done on a structured proforma.The work has been reported in line with the strengthening the reporting of cohort, cross-sectional, and case-control studies in surgery (STROCSS) criteria [8] .

Statistical analysis
The mean value of the overall NEI-VFQ25 score and the value of each subscale score was computed.The values of the composite score and subscale scores were calculated for each KC category and control group.Descriptive analysis was presented in the form of mean SD.ANOVA, independent t-test was the statistical test of significance that was employed.Similarly, correlations between parameters were calculated using Karl Pearson's correlation coefficient.P-value less than 0.05 was considered statistically significant (P < 0.05).SPSS version 20 was the statistical tool employed for the data analysis.

Results
This study consisted of 73 subjects (35 KC subjects and 38 control subjects).Out of 35 KC subjects, 22 males and 13 females were included in the study.Similarly, out of 38 age and sexmatched control subjects, 24 males and 14 females were included in the study.The difference in mean age between the case and control group was not statistically significant (P > 0.05, t = − 0.687) with the t-test as shown in Table 1.
According to Amsler-Krumeich grading the eye with less severe KC, there were 22 eyes in Stage 1 (62.9%),11 cases in Stage 2 (31.4%), 2 eyes in Stage 3 (5.7%),no eyes in Stage 4. Also grading the eye with more severe KC there were 7 eyes in Stage 1 (20%), 15 cases in stage 2 (42.9%), 13 eyes in stage 3 (37.2%),and no eyes in stage 4. Mean best corrected HCVA was worse in the KC group both in the better eye and worse eye while compared with the control group (P < 0.001).Contrast sensitivity was also worse in the KC group when compared to the control group (P < 0.001) as shown in Table 1.

QoL score distribution
The mean scores of all of the subscales of QoL were found to be less than in the KC group when compared with the age and sexmatched control group and the difference was statistically significant (P < 0.001).The mean composite score for the KC group was 66.67 8.63 and for the control group was 93.65 2.39 with P < 0.01.And the mean difference was found to be statistically significant for all subscales and the composite score of QoL (P < 0.01) as shown in Table 2 and Figure 1.
QoL score and scores of all 12 subscales were compared between KC subjects using spectacles and subjects using contact lenses for refractive correction.There was a highly significant difference in the mean composite score of QoL between these two groups.The mean composite score for group 1 (spectacle wearer) was 67.86 7.99 and that of group 2 (contact lens wearer) was 58.63 4.26 with P < 0.01 (independent t-test) as shown in Table 3 and Figure 2.
QoL score and scores of all 12 subscales were compared among two groups of KC; the first group includes KC subjects with disease duration of less than 5 years and the second group includes KC subjects with a disease duration greater or equal to 5 years.The overall composite score was found to reduce significantly as disease duration increases.The mean composite score for group 1(< 5 year) was 71.46 7.69 and that of group 2 ( > 5 year) was 59.98 5.73 with P < 0.01 (independent t-test) as shown in Table 4.
QoL score and the scores of all 12 subscales were compared among three groups of KC in reference to the worse eye as well as better eye of the subject namely group 1 including all KC subjects having grade 1 KC, group 2 including all KC subjects having grade 2 KC, group 3 including all KC subjects having grade 3 KC.There was a significant reduction in the composite score of QoL as the grade of KC increased and the finding was statistically significant (P < 0.01) (ANOVA test) in reference to both worse and severe eye as shown in Table 5.
During the co relational analysis, the composite score of VR QoL was moderate negatively co-related with HCVA of the better eye as compared to the worse eye, that is, (r = − 0.663, P < 0.001) and (r = − 0.539, P < 0.001) respectively, whereas moderate positively correlated with contrast sensitivity score of better eye (r = 0.779 P < 0.001) and worse eye ( r = 0.637, P < 0.001) respectively, HCVA of better eye had modest and statistically significant negative correlation with general health score (r = 0.465) (P < 0.005), general vision score (r = − 0.523) (P < 0.001), ocular pain score (r = − 0.586) (P < 0.01), near activities score (r = − 0.5529)(P < 0.001), distant activities score   Nepalese version of the NEI-VFQ 25 questionnaire to collect QoL scores.NEI-VFQ-25 subscales are multidimensional and designed to evaluate the impact of visual problems on general health, general vision, physical functioning, emotional wellbeing, and many more.
The mean age of subjects in the KC group was 23.94 7.68, ranging from 15 years to 51 years.This study implies that KC strikes the Nepalese population in early adulthood (the peak education, earning age of a subject).In a study conducted by Aydin et al. [9] mean age of KC subjects was 29.36 10.60.Mahdaviazad et al. [10] conducted a similar study and the mean age of KC subjects was 28.6 7.6.The mean log MAR HCVA of the better eye was 0.22 0.20 and of the worse eye was 0.40 0.23 in the KC group with P < 0.001 (paired t-test).In a study conducted by Sevda et al. mean log MAR visual acuity was 0.21 0.23 log MAR for the better eye and 0.4 0.33 log MAR for the worse eye and this finding was comparable with our study [9] .In a study by Panthier et al. [11 ] mean log MAR HCVA for better eye was 0.43 0.45 and the mean log MAR HCVA for the worse eye was 0.84 0.50 with P < 0.001 (paired t-test).
Vision-related QoL score was calculated in 12 subscales and the overall composite QoL score for each individual of both KC group and control was determined.Scores of all subscales along with composite score was found to be lower in the KC group as compared with the control group and the difference was statistically significant for all subscales with (P < 0.001) calculated with t-test.The difference was more evident for the general vision score, distant vision score, near vision score, mental health score, and dependency score.Whereas difference was less evident for the general health score, peripheral vision score, and color vision score.The large differences in the scales that measure visual function (distance and near activities score) and in the mental health and role difficulties scores are very informative.This indicates that KC patients perceive a loss of function disproportionate to that reflected by clinical measures such as visual acuity.Most importantly, this loss of function may lead to a perceived impairment in the ability to perform social duties reflected in the mental health and role difficulties scores.Kurna et al. found significant differences in the mean score of general health score, general vision score, ocular pain score, near vision score, mental health score, role difficulty score along with composite score between KC and control subjects with P < 0.01 which gives clear evidence in support of findings of our study.In the study by Kurna et al. there was no significant difference in the mean score for dependency scale and social functioning scale [9] .Roustaei et al. in a similar study found a significant difference in mean scores of 11 subscales and composite scores between the case and control group with P < 0.01 except the mean score of the color vision scale which did not show a significant statistical difference between the case and control group [10] .On comparing the scores of all subscales of our study with the scores CLEK study, the scores of KC subjects in all subscales were lower in our study than in the CLEK study [12] .
Contact lenses are one of the better solutions to correct refractive errors induced by KC.Contact lens fitting on a conical cornea smooths out the highly irregular optical surface of the cornea and improves visual acuity considerably.The quality and quantity of vision is far better than with spectacle lens correction [13] .Success in contact lens usage in the KC patients may increase the visual acuity and vision-related QoL.In a study evaluating KC patients using RGP lenses, the NEI-VFQ-25 composite score was 79.2 and KC was associated with lower scores in dependency, mental health, and ocular pain categories.In the study by Kurna et al.NEI-VFQ-25 composite score was 75.4 in the KC group of contact lens users.Although not significantly different (P > 0.05), the NEI-VFQ-25 subscale scores of distance vision, vision-specific mental health, role difficulties, social functioning and dependency, and color vision subscale scores of the patients using contact lenses were better than the patients who do not use contact lenses.Meanwhile, general vision, ocular pain, near vision, and peripheral vision scores were worse in the patients using contact lenses (P > 0.05) [9] .In contrast with the above-mentioned study in our study we found a decrement in the QoL scores in all subscales and composite score in contact lens users as compared with spectacle users.The mean score of the ocular pain scale and composite scales were significantly lower in contact lens users than in spectacle users with P < 0.01.This contradictory finding of reduced QoL in Nepalese KC contact lens users than spectacle users might be due to the small sample size of contact lens users taken in our study.Moreover, most Nepalese KC patients usually were contact lenses only after a significant reduction of visual acuity below function level, that is, only after reaching the advanced/ severe stage of KC.All contact lens users recruited in our study were in the advanced stage of KC as a result of which we obtained reduced QoL scores in contact lens users than spectacle users.Likewise, the fitted contact lens was all of traditional RGP design not of modern design of rigid lens like rose K, mini-sclera lens, custom design, etc., or other KC specific designs.
QoL scores of all subscales were calculated in reference to the duration of the disease.In our study, there was a highly significant reduction in QoL scores in most of the subscales along with the overall score when disease duration exceed more than 5 years when compared with the score of subjects with disease duration less than 5 years of age.Similarly while comparing scores among the various grades of KC the VR-QoL was found to be poor for severe condition in reference to both better and worse eye.Due to progressive nature of the condition as duration of disease increases the severity of the disease also increases which may be playing a role in degrading QoL scores.The composite score, general vision score, peripheral vision score, driving score, social functioning score, distant activities score, and near activities score showed significant difference in mean scores with P < 0.001.Mental health score, color vision scale, and ocular pain score also showed significant differences between the two categories of disease duration with P < 0.05.Roustaei et al. in a similar study found significant differences in scores of all subscales when comparing the scores between the subjects having disease duration greater than 5 years and less than 5 years.Scores of all subscale was lower in group with disease duration longer than 5 years with P < 0.05.The finding of our study is in strong agreement with the findings of the Roustaei et al. study [10] .So the above findings suggested us that, similar to various chronic eye diseases like ARMD, glaucoma as the disease progresses the vision-related QoL scores gradually decrease, likewise in Nepalese patients with KC as the duration of KC increases the QoL was found to decrease significantly suggesting the chronic progressive nature of the disease with lifelong impact on eye health and vision-related of QoL of an individual [12] .
Our optimal visual functioning is dependent more on the better eye as compared to the worse eye.All the QoL parameters were more correlated with the visual status (HCVA and CS) and visual functioning of the better eye compared to worse eye in correlational analysis which is in agreement with study done by Kurna et al. so visual parameters of better eye are crucial for determining vision related QoL of a KC subject.So optimizing vision and visual quality in better eye might play significant role in improvising vision related QoL.

Limitations of the study
We outlined the following limitations in our study.The Questionnaire used for the study is NEI VFQ 25 which is found less reliable for the control group.Similarly, Change in QoL in subsequent follow-up cannot be measured as this is a cross-sectional study with a small sample size.The Keratoconus Outcomes Research Questionnaire (KORQ) is the only validated KC-specific questionnaire, had the most superior psychometric properties and found to be more reliable predictor of vision-related QoL as compared to NEI-VFQ 25 so KORQ could have been better questionnaire for accessing the QoL.

Recommendations and practical implications
• QoL can be monitored to evaluate the impact of disease on physical, social, and psychological aspects of the life of a person.
• QoL score can also be used as a subjective tool to monitor the progression of KC. • QoL can be taken as a reference to evaluate the effect of certain treatment modalities of disease.

Conclusion
This study concluded that the vision-related QoL is lower in KC subjects as compared to normal age and sex-matched individual measured NEI-VFQ 25 questionnaire.The QoL of an individual was found to reduce gradually as the severity and duration of the disease increased.Similarly, contact lens-using Nepalese subjects have a poor vision related QoL compared to spectacle-wearing Nepalese subjects.Our study findings suggested that vision and visual function parameters in the better eye is the most important parameter affecting VR-QoL in KC subjects and has major impact in patient's level of visual functioning and corresponding VR-QoL compared to worse eye.So KC patients should maintain the best vision that they can have to keep VR QoL higher.

Figure 2 .
Figure 2. Line graph showing the comparison of quality of life scores between spectacle wearer and contact lens wearer.

Table 1
Demographic data of the subjects enrolled in the study.

Table 2
Comparison of Quality of life scores between keratoconus group and control group.
Figure 1.Line graph showing comparison of quality of life scores between keratoconus group and control group.

Table 5
Composite Quality of life score among 3 groups of keratoconus in reference to better eye and worse eye.

Table 6
Correlations between Quality of life subscales of NEI-VFQ 25 and different visual function parameters.