A cross-sectional study on vision-related quality of life in patients with ocular GvHD

Abstract

Ocular GvHD affects about 40–60% of patients receiving bone marrow transplantation. Ocular complaints worsen quality of life (QoL), which, besides survival time, is a primary end point in a patient's follow-up. The aim of our study was to assess the ocular surface status and vision-related QoL (VRQoL) and explore the potential determinants in VRQoL in patients with chronic GvHD with ocular involvement. In this cross-sectional study, we investigated 40 patients with ocular GvHD after allogeneic hematopoietic stem cell transplantation assessing ocular symptoms and signs, VRQoL and ophthalmologic parameters. The median age was 52.1 years; 32.5% were females. Most of them presented a multiple organ involvement. Ophthalmological parameter examinations were on average abnormal. Corneal staining was severe/very severe in 25%; conjunctival staining in 10% of subjects. The worse QoL scores were on ‘general vision’, ‘ocular pain’, ‘vision-specific mental health’ and ‘vision-specific role difficulties’. Both symptoms and sign scores indicate poor VRQoL. A lower VRQoL was related to schooling level, job position, underlying disease and extracorporeal photopheresis. Corneal staining, Schirmer and tear film breakup time were negatively associated to visual function-related subscales. An accurate ophthalmological and VRQoL assessment should be mandatory for a long time to promptly recognize early signs of ocular suffering, and to prevent irreversible ocular complications.

Introduction

In the past decades, interest in health-related quality of life (QoL) in patients treated with bone marrow transplantation has increased; and to date it is considered, besides survival time, a primary end point in the follow-up evaluation of cancer treatment.¹

International guidelines recommend a multidisciplinary approach to supportive care and management of the organ-specific complications of the chronic GvHD (cGvHD).² The main purpose of the treatment is to obtain the effective control of GvHD while minimizing the risk of drug toxicity and relapse. Moreover, the guidelines underline the important role of QoL perception recommending the assessment of QoL in all patients.²

Ocular GvHD (oGvHD) has protean clinical manifestations, affecting multiple parts of the eye including conjunctiva, lacrimal gland, cornea, lid and vitreous.³

oGvHD affects about 12–17% of patients in the acute setting and 40–60% in the chronic setting.⁴ The most frequent ocular manifestation of GvHD is dry eye syndrome (DES), observed in 69–77% of patients with chronic systemic GvHD.⁴ The National Institutes of Health (NIH) classifies DES with a scale ranging from 0 (no dry eye symptoms) to 3 (pain and visual loss significantly affecting daily living).⁵ When untreated, DES can cause advanced ocular complications that may become irreversible and lead to permanent visual loss affecting daily living and QoL.^{6, 7, 8}

The aim of our study was to assess, in patients with ocular cGvHD, the ocular surface status and vision-related QoL (VRQoL) and explore the potential determinants of VRQoL in these cGVHD patients with ocular involvement under stable treatment for at least 3 months.

Materials and methods

This cross-sectional study was conducted at the teaching Hospital of Pavia. The study was approved by the local Ethics Committee. Patients gave their written consent before inclusion.

Patients were recruited consecutively from January to June 2013.

Eligibility criteria were cGvHD with oGvHD showing DES (at least grade 1 of the NIH Dry Eye Severity Grading Scheme)⁵ with a stable systemic and topical therapy lasting at least 3 months; age 18 years or older; to be able to read and complete QoL questionnaires; and none of the following: concomitant ophthalmic infections, retinal disease, ocular hypertension disease, any systemic or ocular treatment change in the preceding 3 months, or any systemic or ocular surgery in the 3 preceding months (including cataract surgery).

To reduce the variability in clinical assessments, patients were evaluated by the same ophtalmologist. Objective findings included best-corrected visual acuity for distance, Schirmer test (without local anesthesia), assessment of tear film using the tear film breakup time test (expressed as mean value after three measurements), biomicroscopy of the anterior and posterior segment, corneal fluorescein staining and conjunctival lissamine staining, both evaluated following the Oxford scheme.⁹

QoL was assessed using National Eye Institute-25 items Visual Function Questionnaire (NEI VFQ-25) and Glaucoma Symptom Scale (GSS) (Figure 1).^{10, 11}

Figure 1

Flow chart of NEI VFQ-25 and GSS.

Descriptive statistics were produced for all variables. Ocular signs and symptoms are reported only for the right eye. Groups were compared with parametric or nonparametric tests for continuous variables, and with Fisher exact test for categorical variables. Correlation between continuous variables was assessed by means of Pearson’s or Spearman’s coefficient. Median regression was used to estimate the association between QoL and ocular signs/other predictors; clustering per patient was taken into account. Given the exploratory nature of these multiple comparisons, we set the statistical significance at 0.01.

Results

Forty patients were enrolled. Briefly, all were Caucasian; 27 (67.5%) were men; median age was 52.1 (44.8–60) years; most of them were married (82.5%); and had a middle–high educational level (70.5%). After bone marrow transplantation, 60% had become unable to work. Most patients suffered from AML and multiple myeloma (see Supplementary Table 1).

Most patients had multiple, complex, systemic therapies: 85% were under immunosuppressive therapy (anti-metabolites, calcineurin inhibitors and/or steroids), 30% were under calcineurin inhibitors and steroids therapy, and the majority of patients were under systemic antibiotic, systemic antiviral and systemic antifungal therapy, with a median of daily tablets/pills of 8.5 (interquartile range 4.5–11.5).

About ocular therapy, median of eye drops instillation for day was 5.5 (interquartile range 3–10.5), 80% used tear substitutes (hyaluronic acid 0.2–0.4% five times for day and carbomer at night time) and 55% were under platelet lysate treatment (TID). Only two patients used topical fluormetholone 0.1% once a week.

Ophthalmic examinations are reported in Supplementary Table 1.

QoL results are reported in Table 1. The worst scores obtained with NEI VFQ-25 were ‘general vision’, ‘ocular pain’, ‘vision-specific mental health’ and ‘vision-specific role difficulties’. The GSS questionnaire revealed low scores in both subscales.

Table 1 Quality of life questionnaires results

Potential determinants of NEI VFQ-25 total mean score/GSS symptoms score/GSS function score can be found in Supplementary Table 2. Concerning the association between QoL and ocular signs, most QoL dimensions were directly associated (P<0.001) with objective ocular signs (Schirmer, corneal staining and tear film breakup time test; Supplementary Table 3).

Discussion

As the life expectancy of patients treated with bone marrow transplantation has increased, it is very important to promptly recognize and treat all GvHD manifestations, including ocular involvement.

In the past years few papers have investigated the ocular surface status and the impact of oGvHD on patients' QoL.¹² A recent review recommends close monitoring of the ocular condition as ‘with timely diagnosis, irreversible (ocular) damage can be avoided’.¹³ Patients who develop ocular symptoms need close ocular supportive care focused on improving the ocular surface moisture and in decreasing inflammation. This would reduce ocular surface discomfort ameliorating the patient’s QoL.

Therefore, we investigated our patients not only by a careful ophthalmic assessment of corneal and conjunctival signs but also with a specific questionnaire on symptoms to determine the discomfort actually perceived by patients.

The patients included in this study had a diagnosis of ocular surface disorders about 7.5 months after allogeneic hematopoietic stem cell transplantation. These data are in line with a previous study.¹³

The overall QoL of our patients was reduced both when measured with the NEI VFQ-25 questionnaire (which is ‘general’ vision specific) and with the GSS questionnaire (which is symptom and function specific); this is in agreement with a recent study on a smaller cohort of patients.¹² However, in that study the ocular surface disease index questionnaire (measuring primarily ocular surface status) was used.

In fact, we observed a significant association between corneo/conjunctival signs and general vision, ocular pain, near activities and GSS symptoms. This is in line with the limitation in daily and recreational activities (vision-specific role dependency), especially outdoor, that our patients report (notably, despite an on-average normal visual acuity), and with that reported by others.¹² This is particularly relevant as these patients are suffering from a long period of illness and intensive treatments, and feel a strong desire to return to pre-transplant daily life.

It is worth noting that, unfortunately, even if ocular surface disease has a negative impact on our transplanted patients, to date there are no effective preventive strategies for oGvHD although current therapeutic options consist of symptomatic treatment regimens aimed at alleviating the symptoms and at preventing irreversible damage.

Our finding of a significant positive association between schooling level and impact on QoL is probably related to a more sophisticated capacity for introspection.

On the contrary, the number of tablets per day strongly affects QoL; this is probably due to the chronic stress generated by the daily pill consumption and its interference with daily activities, which is probably an obstacle to the return to a normal social and working daily life.

As expected, systemic steroid therapy has a negative impact on the quality of vision, probably due to the co-occurrence of cataract and ocular hypertension, even though it did not affect the ocular symptoms (probably because it reduces the ocular inflammation caused by oGvHD). In fact, most patients presented with more severe GvHD and were extensively treated with steroids.

A number of limitations need to be acknowledged. First, the number of patients examined is too small to draw definitive conclusions and to allow subgroup/multivariate analyses other than with an exploratory aim; however, this is the largest patient sample studied so far in terms of both QoL and clinical signs of oGvHD. Also, we did not follow our group over time, to assess the changes in signs and symptoms.

In conclusion, oGvHD influences QoL in terms of general vision, ocular pain and some vision-specific activities, explaining its impact on daily activities. An early and careful ophthalmologic evaluation associated with a specific and complete quality of vision questionnaire provides a whole ‘picture’ of the actual ocular condition, including the effective quality of vision perception: patients complain about a worse quality of vision early, even when ocular objective signs are still normal.

Considering the current guidelines (which highlight the important role of QoL perception),² an accurate ophthalmological assessment that is comprehensive of a rigorous evaluation of quality of vision should be included in the care of oGvHD patients, independent of actual severity of ocular symptoms; this might help in promptly recognizing the early signs of ocular suffering, in rapidly capturing a worsening of QoL and in preventing irreversible ocular complications. However, this should be confirmed in further, prospective studies.