|Year : 2014 | Volume
| Issue : 3 | Page : 225-231
Quality of life in non-infectious uveitis patients on immunosuppressive therapy
Sheik Kaleemunnisha, S. Sudharshan, Jyotirmay Biswas
Department of Uveitis, Medical and Vision Research Foundation, Sankara Nethralaya, Chennai, India
|Date of Web Publication||19-Jun-2014|
Dr. S. Sudharshan
Medical Research Foundation, 18, College Road, Sankara Nethralaya, Chennai - 600 006
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Purpose: To assess visual function and vision related quality of life in patients with non-infectious posterior or panuveitis treated with immunosuppressives.
Materials and Methods: Forty-three patients with non-inflammatory posterior or panuveitis were enrolled in this prospective study. All subjects underwent a detailed interview, complete ophthalmic examination, quality of life assessment using National Eye Institute Visual Function Questionnaire (VFQ-25), visual function evaluation (visual acuity and visual field) at baseline and at a sixth month follow up visit.
Results: The mean NEI-VFQ 25 composite score of the subjects with posterior or panuveitis was 58.0 (±24.1). There was a statistically significant improvement (P = 0.004) in the composite score following treatment from 58.0 (±24.1) to 74.3 (±22.0) with effect size of 1.03. The psychological well-being and general health subscales showed significant improvement in the mean score following immunosuppressive therapy. While considering the visual function tests, there was a three-line improvement in the visual acuity score and changeover in the visual field severity from moderate to early defect with corresponding improvement in the visual field pattern. Though most of the patients complained of side effects such as tiredness, gastrointestinal upset and weight gain, there was improvement in the general health subscale.
Conclusion: The significant improvement in the general health subscale despite side-effects shows that the benefit of immunosuppressive outweighs the risks of the therapy and this may also reflect the relatively low impact of these side-effects on the quality of life. This study shows that the use of immunosuppressives improves the quality of life of the individual.
Keywords: Immunosuppressives, Corticosteroids, Non-Infectious Uveitis, Quality of Life, Visual Function Questionnaire
|How to cite this article:|
Kaleemunnisha S, Sudharshan S, Biswas J. Quality of life in non-infectious uveitis patients on immunosuppressive therapy. Middle East Afr J Ophthalmol 2014;21:225-31
|How to cite this URL:|
Kaleemunnisha S, Sudharshan S, Biswas J. Quality of life in non-infectious uveitis patients on immunosuppressive therapy. Middle East Afr J Ophthalmol [serial online] 2014 [cited 2021 Oct 19];21:225-31. Available from: http://www.meajo.org/text.asp?2014/21/3/225/134675
| Introduction|| |
Patients with uveitis can have significant ocular morbidity due to the disease itself and due to the drugs used in their management. Infective uveitis usually responds well to specific anti-infective agents and doesn't last long and rarely causes recurrences. Non-infective uveitic entities are known to be recurrent and needs long term therapy with steroids and non steroidal immunosuppressives.
Uveitis and immunosuppressive drugs
Non-infectious posterior or panuveitis such as multifocal choroiditis, Vogt Koyanagi-Harada disease, Behcet's disease are known to be recurrent and require long term therapy with systemic corticosteroids. Although systemic corticosteroid is usually effective for controlling ocular inflammation, dose related side effects of corticosteroids such as hypertension, diabetes, hypercholesterolemia, and osteoporosis necessitate targeting daily doses of steroid to less than 10 mg when the drug is needed on a chronic basis.  In patients who have shown inadequate response to corticosteroid therapy, or developed unacceptable side-effects, other non-steroidal immunosuppressive drugs are recommended.  Non-steroidal immunosuppressive agents allow for improved control and decrease risk of corticosteroid induced side effects.  Although immunosuppressive drugs have some side effects, their use in the setting of ocular inflammation under proper monitoring in a controlled environment has been justified.  Long-term therapy with these drugs may affect the patients' sense of well-being although there are others who oppose immunosuppressive therapy.
Subjective wellbeing of uveitis patients
Schiffman et al.,  described vision and health related quality of life in 76 patients with various types of uveitis and concluded that uveitis has a wide effect on vision and health related quality of life (QOL)  of the individual.
Immunosuppressive medication (includes corticosteroids and/or corticosteroid sparing agents) remains the main stay of therapy in non-infectious posterior uveitis. It can result in both systemic and ocular complications.  Although immunosuppressive medication may be tolerated by patients, their effect on the vision and health related quality of life also needs to be considered. There are very few studies related to visual function and vision related quality of life in patients on immunosuppressives in India. 
The global goal of eye care is to improve the QOL of visually impaired people. In this study, we evaluate visual functions, vision related quality of life issues in patients with non-infectious posterior or panuveitis who were undergoing immunosuppressive therapy.
Patients and methods
Consecutive patients presenting with active non-infectious posterior or pan uveitis attending the Uveitis clinic at a tertiary eye care center were enrolled in this prospective study. All volunteers were appropriately informed before their participation in the study and written informed consent was obtained. Following the agreement to participate in the study, all patients underwent a detailed interview, complete ophthalmic examination, quality of life assessment, and visual function evaluation. All the tests were repeated at 6 month follow up. This study was approved by the Medical and Vision Research foundation Institutional Review Board.
- Non-infectious posterior or panuveitis
- Age >15 years
- No current or previous history of immunosuppressive medication use
- No current or previous ocular surgery or pathology
- Stable treatment regimen/combination during the period.
- Posterior or panuveitis with infective etiology
- Long term other systemic and immunosuppressive medications
- Follow up <6 months.
| Materials and Methods|| |
After detailed case history, the ocular examination was performed by one of the investigator, masked to the outcome of QOL and visual function assessment. Anterior segment and dilated posterior segment examinations were carried out. Standardization of Uveitis nomenclature (SUN) working group classification  was used to grade activity. Fundus photography, fundus fluorescein angiography, ultrasound and optical coherence tomography were performed as required.
VKH, sarcoidosis has both ocular and systemic manifestations. Other posterior uveitic conditions such as serpiginous choroiditis or multifocal choroiditis are known to be recurrent and are usually bilateral although asymmetrical.
Our protocol is to treat these vision-threatening conditions with systemic therapy although supplementary local therapy such as periocular steroids may help. An internist's clearance was obtained before starting systemic immunosuppressive medication.
Visual function assessment
Best-corrected LogMAR visual acuity score for individual letters was measured with the ETDRS chart designed to test at 4 meters. Visual field testing was performed using the Humphrey visual field analyzer with the 30-2 strategy. Visual field reports with unreliable scores >33% of fixation loss, >20% of false positive or false negative responses were excluded from the study. The severity and pattern of visual field defect were graded using Hodapp Anderson Parrish classification (HAP)  and Optic Neuritis Treatment Trial Classification (ONTT)  , respectively.
Quality of life assessment
Vision related quality of life (VR-QOL) was evaluated using the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25). NEI VFQ-25 is a vision specific quality of life instrument derived from a multi-condition focus group process. It measures QOL based on visual disability and how the disability affects the well-being and emotional response. The items in the questionnaire were assigned to the four dimensions of QOL-Functional, Social, Physical, and Psychological.  Pre-treatment and 6 months after treatment, patients were asked to complete the NEI-VFQ-25 form that was administered by interviewer (one of the investigator). The patients completed the questionnaire unless their vision was too poor to read. The responses of patients for each question were transformed to a ''0 to 100'' scale using a standard scoring algorithm. During the follow up visit, patients were asked open ended questions regarding the side-effects they perceived after initiation of the therapy.
Collected data were entered into a Microsoft Excel spreadsheet (Microsoft Corp., Redmond, WA, USA). The statistical analysis was performed using SPSS version 15.0. Descriptive statistics were calculated for all variables of interest. The 2-sample Kolmogorov-Smirnov test was used to test normality. Paired t-test was used to compare mean of the pre- and post-composite score, mental health, role difficulty, visual acuity, mean deviation. Wilcoxon sign rank test was applied for general health, general vision, near activities, distance activities, ocular pain, social functioning, dependency, driving, color vision, and peripheral vision. The Mann-Whitney test was performed for independent non-Gaussian parameters. Spearman's correlation coefficient was used to determine the relation between two parameters. Linear regression was performed to investigate the factors influencing composite score and mean deviation. The responsiveness of the VFQ25 questionnaire to treatment and the accompanying change in vision was evaluated calculating the effect size (used to determine the magnitude of change in the pre and post composite score).
For dependent sample, effect size (ES) = X difference /S difference,
X difference = Average of difference of paired data
S difference = Standard deviation of the paired data
A P value less than 0.01 was considered statistically significant.
| Results|| |
Forty-three patients with the mean age of 32 (±10) years (range 16 to 52 years) were enrolled in the study. The male-to-female ratio was 2:1. There were 63% (n = 27) of patients with unilateral involvement and 37% (n = 16) with bilateral involvement. The mean duration of uveitis was 2.5 months. In the entire study sample, 79% (n = 34) of the recruited patients had no medical co-morbidity and 4.7% (n = 2) had a thyroid disorder, 4.7% (n = 2) had tuberculosis (TB), 7% (n = 3) had joint pains, 2.3% (n = 1) had diabetic mellitus (DM) and 2.3% (n = 1) had hypertension (HT). Two patients (4.7%) were given additional anti-tuberculosis treatment (ATT) cover due to positive Mantoux and Quanti-FERON results as these patients were about to undergo immunosuppressive therapy for their ocular condition. Patients were on treatment for their systemic ailments.
Out of 43 patients, ocular diagnosis was serpiginous choroiditis in 67.4% (n =29, 11.6% as these were with macular involvement). Vogt-Koyanagi-Harada syndrome (VKH) in 20.9% (n = 9), multifocal choroiditis in 4.7% (n = 2), sarcoidosis in 4.7% (n = 2), acute posterior multifocal placoid pigment epitheliopathy (APMPPE) in 2.3% (n = 1). The diagnoses were made based on clinical presentation and confirmed by fundus flourescein angiography (FFA).
Serpiginous and serpiginous-like choroiditis were differentiated based on presentation. Serpiginous-like choroiditis presents with partly coalescing multifocal lesions and with inflammation while the classical serpiginous choroiditis presents with larger coalescing placoid lesions starting from the disk and peripapillary areas. FFA has also been helpful in supporting the clinical diagnosis and for follow-up to monitor activity.
Treatment at baseline
The decision to initiate the patients on immunosuppressive therapy was decided by the investigator based on the clinical requirements of the patients. Fifty-one percent of the patients initially underwent intravenous methylprednisolone (IVMP) 1G daily for 3 days followed by immunosuppressive therapy. Forty (93%) patients were treated with azathioprine, 2 patients with mycophenolate mofetil and one each with methotrexate and cyclosporine. Among these 4 patients who were on azathioprine and one patient on mycophenolate were prescribed cyclosporine in addition to the baseline treatment as the lesions were active.
After initiation of therapy, patients were reviewed at regular intervals and the examination findings at 6 th month were noted.
Vision related quality of life assessment
The mean NEI-VFQ 25 composite score of the patients with posterior or panuveitis was 58.0 (±24.1) (where "0" is the worst possible score and "100" was the best possible score). Eight of the subscales (global vision rating; difficulty with near vision activities; difficulty with distance vision activities; limitations in social functioning due to vision; dependency on others due to vision; limitations with peripheral and color vision, ocular pain) had mean scores ranging from 49 to 85. The subscales that were most affected were mental health and role difficulties. The single general health rating question had a score of 45.5 (±21.6). The driving subscale was excluded from the composite score if the subject did not respond to the driving subscale.
The follow up rate was 70% (sample size at baseline: 43, follow-up: 30). There was a statistically significant improvement in the composite score following treatment from 58.0 (±24.1) to 74.3 (±22.0) and according to Cohen's, the magnitude of change in the composite score was large (P = 0.004; effect size = 1.03). Three of the subscales (general vision, role difficulty, distance activity) showed statistically significant improvement in the scores with a large magnitude of improvement (P < 0.0005, ES >0.80). Though near activities, social functioning, mental health, dependency subscales had a statistically significant improvement in the scores, the magnitude of change was found to be moderate (ES >0.50). [Figure 1] represents the improvement in the scores of general health and vision related subscales, while [Figure 2] represents the improvement in the scores of psychological well being subscales. The single general health-rating question also showed medium change in the magnitude (P = 0.009, ES >0.573). The driving subscale did not show statistically significant improvement. Ocular pain (comfort), color vision, peripheral vision sub-scales showed a small change in the magnitude (ES < 0.50 and >0.20) [Table 1].
|Table 1: Mean score at the baseline and follow up and the correlation between subscale and composite score|
Click here to view
Though the improvements in the pre- and post- treatment score were significant, while comparing patients with composite score less than 50 (group 1) and greater than 50 (group 2), patients with lower pre-treatment VFQ-25 composite score (group 1) showed a 26 point improvement in the score after treatment while group 2 showed an 11 point improvement.
Linear regression analysis was performed to determine if age, sex, laterality, duration of ocular problem, systemic health condition affected VFQ 25 composite score. There was a moderate negative correlation between the binocular visual acuity and the composite score (r = -0.624, P = 0.000). The duration of the disease was not associated with worse visual acuity or VR-QOL.
Nine of the subscales-general vision, near activities, distance activities, social functioning, mental health, role difficulty, dependency, peripheral vision, color vision showed strong correlation with the composite score [Table 1].
Effect of posterior or pan uveitis on visual function
The mean LogMAR visual acuity in the affected eye was 0.69 (±0.60) log units (Snellen equivalent 4/20). At follow up, the mean visual acuity improved to 0.31 (±0.56) log unit (Snellen equivalent 4/8), a three line improvement from baseline that was statistically significant (P = 0.00).
The baseline average of the foveal threshold, mean deviation and pattern standard deviation were 27.80 dB (±6.07), -9.09 dB (±6.49), and 5.59 dB (±2.9), respectively. At baseline, 40 out of 43 patients underwent visual field testing. Three patients had visual acuity that was too poor to perform visual fields. Post-treatment, there was 4.71 dB improvement in the foveal threshold, 3.28 dB in mean deviation and 2.17 dB in pattern standard deviation, respectively. At follow up, out of 30 patients, 27 patients underwent visual field examination. Three patients had profound visual impairment that precluded visual field testing.
As per HAP visual field severity score, 37.30% had an early defect, 39.2% had moderate defect and 23.5% had severe visual field loss. Visual field pattern abnormalities as per ONTT classification showed cecocentral pattern in 28.3%, multiple foci in 24.5%, paracentral defect in 15.1%, constricted field in 11.3%, generalized reduction in 11.3%, and enlarged blind spot in 9.4% of the patients.
After treatment, 58.6% had early defect, 27.6% had moderate defect, and 13.8% had severe defect [Figure 3]. In the pattern of visual field defect, 28.6% had no visual field defect, 14.3% had cecocentral pattern, 14.3% had paracentral defect, 20% had enlarged blind spot, 11.4% had generalized reduction in sensitivity, and 5.7% had multiple foci and 5.7% had constricted field.
Using SUN criteria, a 2-step decrease in inflammation and improvement in visual acuity of at least two lines was used to define clinical efficacy. At the end of 6 months follow up, 90% had complete resolution of inflammation, 10% had reactivation in this 6 months period and were on treatment for reactivation.
At the end of the follow up at 6 months, 3 patients (10%) were changed to alternative immunosuppressive therapy for recurrence of active lesions, persistence of inflammation and defined as treatment failure.
The majority of the patients complained of tiredness (70%, n =21), gastrointestinal upset (70%, n =21) and weight gain (63%, n =19). 43% (n =13) reported mood swing. Forty percent (n =12) of the patients gave a history of recurrent attacks of headache after using immunosuppressive therapy. Thirty percent (n = 9) reported acne, 26.7% (n = 8) reported joint pain, 20% (n = 6) noticed a difference in the taste of food, 6.7% (n =2) reported alopecia. One patient reported urinary tract infection and one patient reported patches over the body (not related to psoriasis). Six patients had only one side effect while the rest had two or more side effects. Blood counts, liver function test, renal function test, blood sugar, and other lab tests to monitor side effects of these drugs were performed regularly as required. Physician review was performed as required.
| Discussion|| |
Traditional clinical measures of vision provide information regarding the disease process but they may not capture all the important aspects of visual function from the patient's perspective and the effect of treatment on the person as a whole. This shortfall has been addressed in our study by the assessment of Quality Of Life (QOL). We analyzed the effect of immunosuppressive therapy on QOL of the patients with non-infectious posterior/panuveitis.
We found that there was a statistically significant improvement in the composite score from 58.0(±24.1) at baseline to 74.3(±22.0) at follow up with a larger effect size (P = 0.004; effect size = 1.03). The reduction in the inflammation and improvement in the visual acuity showed a corresponding improvement in the quality of life scores. The improvement in the quality of life scores can be attributed to the fact that the initiation of immunosuppressives reduced the disease activity which has possibly indirectly reflected on the quality of life scores.
A study by Sathian et al.,  showed a slight dip in the general health subscale following immunosuppressive treatment due to the side effects. However, in our study, the mean of general health subscale score improvement following immunosuppressive therapy.
Carol et al.,  suggested that the general health subscale question may be treated as a standalone item as it is a robust marker of overall health status in many population based studies. The results of our study concur with Carol et al.'s  in that there was no correlation between general health subscale and composite score and thus the general health subscale question can be considered as a standalone indicator.
The four components of psychological well being-social functioning, mental health, role difficulties, dependency showed moderate to large improvement in the sub-scale scores similar to other studies.  The significant improvement in the psychological well being related subscales proves that the impairment of visual acuity had an imperative impact on the psychological well being indirectly. Emotional or psychological factors also contribute to how well a patient believes he/she can see. Significant improvement in other subscales like general vision, near activities; distance activities following immunosuppressive therapy as reported by others  were also noted in our study. The correlation between composite score and the subscales reflects the functional visual problems which it is proposed to measure. The correlation between the binocular visual acuity and the composite score contrasts with the usual finding that VR-QOL was more closely associated with the better eye visual acuity or worse eye visual acuity.  This suggests that the patient response to the questionnaire was given by considering the real world setting. The patient's perception of their vision over time was positively correlated with changes in visual acuity. Visual acuity was not the only aspect of vision and improvement in visual field can also lead to subjective improvements in vision without any change in the visual acuity. This possibly explains the reason why the correlation between VRQOL and visual acuity was not higher.
Patients who had VFQ-25 scores less than 50 at baseline showed improvement in the scores at follow up after receiving the treatment. This observation may be attributed to the fact that their baseline problems were greater. Both unilateral and bilateral severity of visual impairment had similar effects on vision targeted health quality of life and VFQ25 composite score was also not influenced by gender, laterality, and systemic ailments. Patients had a statistically significant improvement in the visual acuity at follow up (P < 0.0005). Notably, patients who presented with moderate visual field loss with a centrocecal pattern that changed to an early defect and improvement in the visual field pattern following treatment. Considering the mean deviation as a continuous variable, there was a statistically significant 4dB improvement. The mean LogMAR visual acuity of the patients lost to follow up was 0.59 (±0.56) log units (Snellen equivalent 4/16) at baseline and the duration of uveitis disease process was 2.75 months (82 days).
Gastrointestinal upset, tiredness, and weight gain were the major side effects perceived by the majority of the patients. Gastrointestinal intolerance in patients on azathioprine has been variably reported and it was seen in about 70% patients in our study. In spite of the side effects, there was a significant improvement in the pre- and post- general health subscale, which shows that the benefit of immunosuppressive therapy outweighs the risks of the therapy as also possibly because the side effects were transient and tolerable. This may also reflect the relatively low impact of these side-effects on quality of life in the present study.
Baseline QOL values can be reduced when uveitis is active. Although transient and reversible, immunosuppressives can possibly have side effects which may be expected to have an influence on the QOL and might further lower their values. Our study shows that improvement in ocular condition improves the patient's perception of the chronic disease and quality of life and seems to ignore the milder transient side effects. Perhaps the fact that the patients' sense of well being improved because they were no longer on drugs or its side effects, the improvement in the uveitis process may be such that the QOL improved as a result of resolution of ocular inflammation. In general, people fear loss of vision and becoming a dependant, than they dread other tolerable side effects. Hence, we can conclude that with their effect on resolution of uveitis and relief associated with the fact that vision is intact may also contribute to QOL improvement. The use of immunosuppressive therapy for a short duration in the course of the disease and follow up do not irreversibly affect the QOL of the individual, and it does not subsequently worsen.
There are some limitations to our study. A longer term follow-up analysis results of patients on immunosuppressives would have given further insight regarding their quality of life at that point. Seventy percent of patients followed up within 6 months. A heterogeneous collection of posterior segment intraocular inflammation may differ with regard to clinical manifestations, severity, treatment response and prognosis, and an even larger number of patients may compensate for the heterogeneity.
Among the main strengths of this study includes the fact that QOL and clinical information was collected prospectively using standardized protocols. A standard regimen was followed in all patients and was attended to by a single clinician. In addition to tests of significance, we calculated effect size measure to display the magnitude of effects.
| References|| |
|1.||Thorne J, Jabs D, Qazi F, Nguyen Q, Kempen J, Dunn J. Mycophenolate Mofetil therapy for inflammatory eye disease. Ophthalmology 2005;112:1472-7. |
|2.||Hemady RK, Chan AS. Immunosuppressive agents and Non-steroidal anti-inflammatory drugs for ocular immune and inflammatory disorders. Ophthalmol Clin North Am 2005;18:511-28. |
|3.||Lustig MJ. Use of immunosuppressive agents in uveitis. Curr Opin Ophthalmol 2003;14:399-412. |
|4.||Kempen JH, Daniel E, Gangaputra S, Dreger K, Jabs DA, Kaçmaz RO, et al. Methods for Identifying Long-Term Adverse Effects of Treatment in Patients with Eye Diseases: The Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Ophthalmic Epidemiol 2008;15:47-55. |
|5.||Schiffman RM, Jacobsen G, Whitcup SM. Visual functioning and general health statues in patients with uveitis. Arch Ophthalmol 2001;119:841-9. |
|6.||Park K. Park's Text book of Preventive and Social Medicine, 19 th ed. Jabalpur: Banarasidas Bhanot Publishers; 2007. pp. 16. |
|7.||Jabs DA, Rosenbaum JT, Foster CS, Holland GN. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: Recommendations of an expert panel. Am J Ophthalmol 2000;130:492-513. |
|8.||Rathinam SR, Sathian N. Vision and health related quality of life in immunosuppressive treated uveitic population. Tamilnadu J Ophthalmol 2006;44:33-6. |
|9.||Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of Uveitis Nomenclature Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol 2005;140:509-16. |
|10.||Buden DL, Rhee P, Feuer WJ, McSoley J, Johnson CA, Anderson DR. Comparison of glaucomatous visual field defects using standard full threshold and Swedish interactive threshold algorithms. Arch Ophthalmol 2002;120:1136-41. |
|11.||Gordon LK, Goldhardt R, Holland GN, Yu F, Levinson RD. Standardized visual field assessment for patients with birdshot chorioretinopathy. Ocul Immunol Inflamm 2006:14:325-32. |
|12.||Mangione CM, Lee PP. Development of the 25 item National Eye Institute Visual Function Questionnaire. Arch Ophthalmol 2001;119:1050-8. |
|13.||Murphy CC, Greiner K. Cyclosporine verses Tacrolimus therapy for posterior and intermediate uveitis. Arch Ophthalmol 2005;123:634-41. |
[Figure 1], [Figure 2], [Figure 3]