Vision-related quality of life in patients treated for ocular syphilis

Multiple studies have showed negative impact of non-infectious uveitis on quality of life (QoL). Less is understood regarding life experiences in patients with infectious uveitis. We investigated vision-related QoL in individuals who had recovered from ocular syphilis. 32 adults treated for ocular syphilis at a uveitis service in Brazil completed the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25), and a comprehensive ophthalmic examination was performed. Medical records were reviewed to confirm resolution of ocular inflammation for 3 months pre-enrolment, and collect clinical data. The NEI VFQ-25 composite score was low overall (75.5 ± 19.8, mean ± standard deviation), and subscale scores varied from relative lows of 59.1 ± 39.6 (driving) and 60.9 ± 24.5 (mental health), to relative highs of 84.8 ± 21.8 (ocular) and 89.1 ± 21.0 (color vision). Adults aged over 40 years and those with a final visual acuity of 20/50 or worse had significantly lower mean composite and subscale scores. Other clinical characteristics—including gender, HIV co-infection, and type of uveitis—did not significantly influence scores. Our findings, taken in context with previous observations that prompt recognition achieves better vision outcomes, suggest early treatment may improve QoL after recovery from ocular syphilis.

Collection of clinical data.The medical record was used to verify the diagnosis of ocular syphilis, and to confirm that the ocular inflammation had been inactive for at least 3 months prior to enrolment in the study.Additional data that were collected from the medical record included: self-identified gender, age at presentation with uveitis, human immunodeficiency virus (HIV) serology, type of ocular inflammation, type of uveitis, laterality of uveitis, presenting best-corrected visual acuity (BCVA), and treatment regimen.The type of uveitis was defined anatomically, using the Standardization of Uveitis Nomenclature (SUN) classification 25 .Isolated papillitis was classified as posterior uveitis for the purposes of the statistical analysis.
A comprehensive ophthalmic evaluation was performed, including measurement of BCVA, slit-lamp examination and indirect ophthalmoscopy with pupillary dilation.The BCVA of the better seeing eye was used for evaluating associations between clinical characteristics and vision-related quality of life, since this is strongly correlated with self-reported visual disability 26 .A BCVA of 20/50 or worse defined vision loss.
Vision-related quality of life assessment.The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was used to assess the patient-perceived vision-related quality of life 24 .A validated Portuguese language interview format version was employed; this had 39 total items, including 14 additional items from the original 51-item NEI-VFQ 27 .
The NEI VFQ-25 generates 12 subscales: general health, general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, visionspecific dependency, driving, color vision, and peripheral vision.Higher scores indicate a better quality of life; lower scores indicate a worse quality of life.Following the standard instructions for analysis of the NEI VFQ-25, scores for each item were converted to a 0 to 100 scale, with the lowest and the highest possible scores set at 0 and 100 points, respectively.Items within each subscale were averaged to give 12 subscale scores.A composite score was calculated by averaging all subscale scores with the exception of the general health score.

Statistical analysis.
Statistical analysis was performed using Microsoft Excel 16.64 for Mac (Microsoft Corporation, Redmond, WA) and SPSS 16.0 for Windows (SPSS Incorporated, Chicago, IL).Continuous variables were expressed as the mean ± standard deviation (SD).Categorical variables were expressed as absolute and relative frequencies.Student's t-test, Fisher's exact test, Fisher-Freeman-Halton's exact test, and Mann-Whitney U test were used to compare groups.A p-value of less than 0.05 was taken to indicate a statistically significant difference between groups.
Table 1 presents clinical characteristics of the study participants, and shows results of the analysis of vision outcomes.Across the 32 patients, initial BCVA in the better seeing eye was better than 20/50 in 19 (59.4%), 20/50-20/150 in 6 (18.7%), and 20/200 or worse in 7 (21.9%).Following treatment and after complete resolution of the ocular inflammation, BCVA in that eye of the patient was better than 20/50 in 26 (81.3%), 20/50-20/150 in 5 (15.6%), and 20/200 or worse in 1 (3.1%).None of the clinical characteristics that were recorded (including demographics, type of uveitis, presenting BCVA, and treatment) were significantly associated with the final BCVA in the better-seeing eye (p > 0.05).
Mean composite score and subscale scores of the NEI VFQ-25 completed by the 32 patients are presented in Table 2. Taking the patients as a total, mean composite score was 75. 5  In comparison to patients with good final BCVA, those with a final BCVA of 20/50 or worse had significantly lower mean scores for general vision, near activities, distance activities, social functioning, mental health, role difficulties, and dependency subscales, as well as a significantly lower mean composite score (p < 0.05).For a subset of these subscales (distance activities, social functioning, mental health, and role difficulties), lower mean scores were also significantly associated with an initial BCVA of 20/50 or worse.In comparison to younger adults (40 years and less), middle and older aged adults (over 40 years) had significantly reduced scores for near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, and peripheral vision subscales, plus a significantly lower mean composite score (p < 0.05).Other clinical characteristics (including demographics, type of uveitis, and treatment) did not significantly influence mean composite score or subscale scores (p > 0.05).The differences in scores overall and by age, and initial and final BCVA are illustrated in Fig. 1.

Discussion
Non-infectious uveitis has been shown to reduce an individual's quality of life substantially [9][10][11][12][13][14][15][16][17] .There is less clarity around infectious uveitis: three studies of ocular toxoplasmosis drew different conclusions [21][22][23] , and a study of herpetic anterior uveitis showed a modest effect 20 .We assessed quality of life in a group of 32 patients who had recovered from ocular syphilis-manifested as intermediate, posterior or pan-uveitis-following standard treatment with antibiotics, supplemented with corticosteroid in approximately two-thirds.We found that middle and older aged adults, over 40 years when diagnosed and treated, experienced a lower overall quality of life than younger adults.Persons with reduced BCVA, reading 20/50 or worse after resolution of the uveitis, also reported reduced composite quality of life in comparison to those without vision loss.
Ocular syphilis has a readily available and inexpensive, safe and effective treatment that cures the condition 5 .On that basis, one might expect no impact on quality of life following treatment.However, our patients had a low mean composite scores (75.5 ± 19.8) when compared with the reference group in the original description of the NEI VFQ-25 (93.0) 24 , as well as groups of middle-aged and older Latinos without visual impairment (86.3 for English-speaking, 85.1 for Spanish-speaking) 28 .However, there may be a delay in reaching the diagnosis of ocular syphilis, and this has been cited as a reasons for poor outcome 29 .Indeed, visual recovery is incomplete in up to one-third of eyes, and a range of complications-cataract, glaucoma, macular pucker, optic atrophy and rhegmatogenous retinal detachment-may result in long-term visual disability 3,4,30 .
Table 1.Clinical characteristics of patients with ocular syphilis (n = 32 individuals) subdivided by bestcorrected visual acuity after treatment and resolution of disease.SD standard deviation, HIV human immunodeficiency virus, BCVA best-corrected visual acuity (in better seeing eye), IV intravenous.a Corticosteroid treatment was oral prednisone in all cases, and one individual also was given a periocular triamcinolone acetonide injection prior to referral and diagnosis of ocular syphilis.Statistical analyses were performed by: b Student's t-test, c Fisher's exact test, d Fisher-Freeman-Halton exact test.We found associations between quality of life scores across seven subscales (including general vision, near activities, and distance activities) in addition to the composite score for BCVA after resolution, and across four subscales (also including general vision, near activities, and distance activities), but not the composite for presenting BCVA.Patients with initial and final BCVA of 20/50 or worse had lower scores regardless of uveitis type and treatment.The same association between BCVA and scores on the NEI VFQ-25 has been reported in studies of other types of uveitis 13,19,31 .It was also noted during development of the questionnaire, with similar correlation for better and worse seeing eyes, especially in subscales related to general vision, near vision, and distance vision 24 .
In patients with ocular syphilis, being aged over 40 years was statistically correlated with lower quality of life.A large cross-sectional study from Germany that included 619 working adults showed a clear age dependency of NEI VFQ-25 scores: the composite score decreased by approximately one point for every decade of life, for adults with and without eye diseases 32 .Lower near and distance activity subscales of visual functioning were observed in patients with Behçet uveitis aged 30 years or older 16 ; and general vision, near activities, and role difficulties subscales were negatively correlated an age of 45 years or more in herpetic anterior uveitis 20 .However, the opposite result of no correlation between age and NEI VFQ-25-derived quality of life scores have also been reported for groups of patients with non-infectious uveitis 11,12,18 and ocular toxoplasmosis 22 .
Limitations of our study include the collection of data at a tertiary referral center, and the inability to recruit all eligible patients, potentially introducing selection bias.Also, discrepancies in sample size may have influenced some results: although we did not observe associations between quality of life, and gender, HIV infection status and type of uveitis, less than 20% of our patients were HIV-positive, 25% were women, and the majority had posterior uveitis.We did not attempt to correlate quality of life scores with ocular complications given the small size of the patient group.Despite these limitations, our study provides unique data on the quality of life in patients who have suffered from ocular syphilis.Given the association we observed between BCVA and NEI VFQ-25 scores, plus previous observations that prompt recognition achieves better visual outcomes 3,33,34 , we speculate that early diagnosis and treatment may result in higher quality of life for individuals with ocular syphilis.

Figure 1 .
Figure 1.Mean subscale and composite scores on the National Eye Institute Visual Function Questionnaire-25 for patients with ocular syphilis (n = 32 individuals) overall and by age, and initial (presenting) and final (postresolution) best-corrected visual acuities.Plots were created in Microsoft Excel 16.64 for Mac.

Table 2 .
Subscale and composite scores on the National Eye Institute Visual Function Questionnaire-25 for patients with ocular syphilis (n = 32 individuals) presented as mean ± standard deviation overall and for different clinical characteristics.HIV human immunodeficiency virus, BCVA best-corrected visual acuity, IV intravenous.Statistical analyses were performed by Mann-Whitney U test, with bold values denoting statistical significance (p < 0.05).
a Intermediate uveitis was not included as this group included one individual.