Introduction:
Vitiligo is defined as an idiopathic, autoimmune condition characterized by destruction of the melanocytes in small or large circumscribed areas of the skin, resulting in patches of depigmentation. Melanocytes are distributed in the epidermis and its appendages, eyes, inner ear and the leptomeninges. Melanocytes in the eye are present within two different layers, the uveal tract and retinal pigment epithelium. Various ocular abnormalities have been noted among vitiligo patients chiefly involving the retinal pigment layers but related studies are very limited extent and none of the studies have focused on probable associations or risk factors for ocular involvement in vitiligo.
Materials and Methods
This was a prospective case control study. All consecutive patients diagnosed with vitiligo were taken as cases. Control group consisted patients with no vitiligo but the same demographic characteristics as the study group.
75 cases of diagnosed Vitiligo were referred from Dermatology department to our department. These patients constituted study group. The demographic features of the patients including age, gender, duration of vitiligo, type of vitiligo as well as the anatomical distribution of the depigmentation macules were noted. Vitiligo patches were distributed on the forehead and scalp, periorbital and perioral areas, neck, trunk, upper and lower limbs, neck, genitalia and non dermatomal locations. A standard ocular examination was performed including best corrected visual acuity assessment, external examination with torch light and slit lamp, gonioscopy and dilated fundoscopy by slit lamp biomicroscopy using 78D Volk lens. Cases with positive findings were documented with anterior segment camera and fundus camera.
Total 75 cases, with same demographic characteristics as the study group, were randomly selected from the Ophthalmology OPD and they underwent the same examination protocol as the other groups. These constituted the control group.
Evaluation of the demographic characteristics of the cases was done which included distribution of cases on the basis of age and gender. The significance (clinical and statistical) of type of vitiligo, duration of the same and demographic characteristics, in respect to ocular involvement in the cases was then studied. Simultaneously the control group with subjects of same demographic characteristics as the study group, was evaluated and their ocular manifestations were tested for significance of the demographic characteristics to rule out factors other than vitiligo as probable cause of ocular changes.
The results were tabulated and charted and chi-square test was employed to calculate the statistical significance of the findings.
Results
Total number of subjects in both case group and control group were 75 (Table 1). Out of 75 cases 58 were under 30 years of age. Only 4 cases of vitiligo were over 40 years of age. Males in case group were 32 as compared to 43 females.
| Table 1: Number of cases and controls |
Number of subjects in case group |
75 |
Number of subjects in control group |
75 |
Total number of vitiligo lesions |
95 |
Duration of vitiligo |
3 months to 65 months |
Number of subjects with iris hypopigmentation |
34 |
Number of patients with angle hypopigmentation |
22 |
Number of patients with fundus changes |
40 |
Number of vitiligo cases with ocular symptoms |
1 |
Periocular and perioral areas were the most common sites of lesion accounting for 29% of cases. 21% cases had the lesion located near the genitalia (Graph 1). 20 out of the 75 cases were diagnosed within the last 12 months of starting the study. Only 3 cases were having a follow up period of more than 5 years. 63 out of the 75 cases of vitiligo had ocular changes. Twenty five (33.3%) had iris hypopigmentation and 23 (30.6%) and 15(20%) cases had fundus and anterior angle changes respectively. Few of the manifestations are shown in figures 1 to 5. Ocular manifestations with respect to age (Graph 2), gender (Graph 3), duration of vitiligo (Graph 4) and location of vitiligo lesions (Graph 5) are shown in various graphs. Peripapillary atrophy is the most common of the fundus changes present in 18 of the 23 cases. Fundus changes are more common in females and in cases in the 11-20 age group (p>0.05). Cases with vitiligo lesion located on face and genitalia had the maximum number of fundus changes (p<0.05). There is however no relationship between duration of lesion and fundus changes (Table 2).
| Table 2: Types of fundus lesions and relation to age, gender, location of vitiligo and duration of vitiligo |
Fundus lesion |
Age in years |
Gender |
Location of vitiligo |
Duration of vitiligo (months) |
11-20 |
21-30 |
31-40 |
41-50 |
F |
M |
Face, neck |
Limbs |
Trunk |
Genitalia |
Others |
1-12 |
13-24 |
25-36 |
37-48 |
49-60 |
61-70 |
Peripapillary atrophy |
7 |
4 |
5 |
2 |
9 |
9 |
6 |
5 |
5 |
5 |
4 |
4 |
0 |
3 |
5 |
6 |
0 |
Temporal crescent |
1 |
0 |
0 |
0 |
1 |
0 |
1 |
0 |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
Diffuse hypopigmentation |
0 |
2 |
0 |
1 |
1 |
2 |
0 |
0 |
1 |
2 |
1 |
0 |
0 |
2 |
0 |
0 |
1 |
Tessellated background |
1 |
0 |
0 |
0 |
1 |
0 |
1 |
0 |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
Comparison of iris changes, AC angle changes and fundus changes are shown in Table 3.
 |
 |
Graph 1: Sites of lesion |
Graph 2: Ocular manifestations with respect to age |
 |
 |
Graph 3: Ocular manifestations with respect to gender |
Graph 4: Ocular manifestations with respect to duration of vitiligo |
 |
Graph 5: Ocular manifestations with respect to location of vitiligo lesions |
| Table 3: Comparison of iris changes, AC angle changes and fundus changes |
|
Cases |
Controls |
Iris hypopigmentation* |
25 |
9 |
Angle changes# |
15 |
7 |
Fundus changes* |
|
|
Peripapillary atrophy |
18 |
1 |
Temporal crescent |
1 |
6 |
Diffuse hypopigmentation |
3 |
3 |
Tessellated background |
1 |
7 |
| *p<0.05, #p>0.05 |
 |
 |
Photo 1: Hypopigmented spots on the retina |
Photo 2: Peripapillary atrophy |
 |
 |
Photo 3: RPE Atrophy |
Photo 4: Iris atrophy |
Discussion
The study group was composed of 75 diagnosed cases of vitiligo with a male to female ratio of 1:1.34, thus indicating a female preponderance. The female preponderance of subjects corresponds with the study undertaken by Wagoner et al[1] for observation of new manifestations in vitiligo in 1983. Though Vitiligo is known to affect both sexes equally,[2,3] there are studies showing female preponderance (perhaps due to greater cosmetic concern in females).[4]
The patients ranged from 11 years to 50 years in age. Age groups between 11 and 30 had the maximum number of cases each having 29 cases accounting for 38.7% of the total cases.
The control group comprised of same number of subjects as study group with the same age and gender distribution as the study group. This was done to evaluate whether age and gender of cases were acting as risk factors for ocular involvement in vitiligo or the ocular changes could only be attributed to demographics of the cases with no relation to vitiligo at all.
Out of 34 subjects with iris hypo pigmentation / atrophy, 25 (33.3%) belonged to the study group with only 9 (12.0%) in control group. This predominance of iris involvement in study group is clinically and statistically significant. Out of 22 subjects with pigmentation of the anterior chamber angle 15(20%) belonged to the study group. This difference is not statistically significant which collaborates with studies that have shown that anterior chamber angle pigmentation increases with age. Of the 40 subjects with fundus changes 23 (57.5%) were in the study group and this difference is also statistically significant with p value being <.05 thus eliminating demographics of the subjects as possible cause of fundus changes.
The present study has no cases with complaints about vision except one in which case nuclear sclerosis explains the diminution. This presentation of vitiligo cases without any ocular symptomatology corroborates with the study of Nordunt and Lerner.[5] The lack of symptoms can be explained by the location of the destructive lesions which lie in the periphery and not near the macula.
The study group had iris hypopigmentation as the most common type of ocular manifestation in 33% of the cases followed by peripapillary chorioretinal atrophy at 22.67%. Hyper pigmentation at the anterior chamber angle and diffuse atrophic patches were also seen. This finding of iris hypopigmentation being the major ocular manifestation in vitiligo parallels that of Biswas et a.[6] 48% of vitiligo cases had no ocular manifestation which is slightly more than the values obtained by Biswas et al[6] and much less than that by Baskan et al[7] who had 77% of the vitiligo positive cases showing no ocular manifestations.
Studies by Wagoner et al[1] had suggested that periocular skin depigmentation as a frequent abnormality in patients with ocular findings and Rosenbaum et al presented a case report suggesting the same,[8] these studies prompted us to include anatomical location of the vitiligo lesions for analysis in this study. Localization of the hypo pigmented lesions on the face primarily periorbital region and the neck were seen in 28.4% of the cases with positive lesions. This was followed by the lesions distributed diffusely all over the body in 21% of the cases. Fifteen (30.6 %) of the cases with ocular lesions had vitiligo lesion located on the face around the orbit and perioral, 24.5 % had lesions located in the genitalia. These percentages are clinically significant thus corroborating the findings in yet another study where concordance between periorbital, genital vitiligo and ocular findings was demonstrated.[7] Individual assessment of the type of ocular manifestation reveals iris and fundus changes to be maximum in cases with lesions located on face and angle changes were more in cases with genital vitiligo.
92% of cases in study group had iris changes before age of 30 years. Similarly more than 90% cases had anterior chamber angle changes before 30 years of age and the changes in the fundus also manifested in cases before 30 years. But these are not statistically significant. Similarly the ocular manifestations show a male preponderance with more that 50% male cases showing eye changes, but though this is clinically significant the p value is >.05 making it statistically insignificant. Thus age and gender cannot be marked as risk factors for ocular involvement in vitiligo.
The duration of the disease varied from 3months to 6years. Most of the patients (59%) presented within 3 years of onset. Twenty cases (40%) were on PUVA therapy at time of being enrolled in the study in the vitiligo group. Iris and anterior chamber angle changes were present in maximum numbers in cases of vitiligo with a recent diagnosis of 12 to 18 months. Fundus changes though were seen more in cases of vitiligo with a diagnosis made 40 to 60 months back. This implies that duration of the lesion may be taken as an indicator of ocular involvement, but these findings were not statistically significant on chi-square test thus corroborating with other studies.[7]
Evidence that the uveal melanocytes and pigment epithelium of vitiligo patients are destroyed was first produced by Albert et al[9] in 1979, they reported various abnormalities in 112 vitiligo patients, including uveitis, retinal pigment epithelial hypopigmentation, chorioretinal scars, pigment clumping and iris transillumination defects. In the same year, a case demonstrating bilateral retinal pigment epithelial changes associated with periorbital vitiligo and seizure was reported.[8] Four years later, Albert et al showed asymptomatic and symptomatic retinal pigment epithelium atrophy in 27% of 223 vitiligo patients, they demonstrated a significantly increased prevalence of nonspecific retinal pigment epithelium hypo pigmentation compared with a control population. Although 25% of cases with RPE atrophy were symptomatic with complaints of nyctalopia, only one of these patients had decreased visual acuity and abnormal ERG and dark adaptation studies which could be attributed to RPE photoreceptor atrophy. A study on clinical pattern of ocular manifestations in vitiligo concurred with findings of Albert et al.[6] They found iris hypo pigmentation as the most common ocular finding in vitiligo cases followed by pigmentation over angles of anterior chamber, RPE hypo pigmentation came third. Most of the cases were asymptomatic with the control group showing a lower incidence of similar ocular changes. Periocular and genital vitiligo have been found to be more commonly associated with ocular involvement.[7]
Studies till now have aimed at addressing the ocular manifestations in vitiligo with very few been done to find out if any particular association predisposes an individual to ocular involvement with vitiligo. Marking out the factors that indicate increased probability of ocular involvement with vitiligo shall aid as a beacon for the ophthalmologist evaluating cases of vitiligo.
Conclusion:
Study of the clinical pattern of ocular manifestations in cases diagnosed with vitiligo reveals that ocular involvement in vitiligo is asymptomatic with most of the cases having no ocular complaints. The lesion are located on the face in majority of the cases with diffuse distribution (vulgaris) being the next most common type of vitiligo. In the eye there occurs primarily the involvement of layers consisting of melanocytes. Iris hypopigmentary changes are the most frequent followed by fundus changes and increase pigmentation of the anterior chamber angle. In the fundus peripapillary chorioretinal atrophy is the most common, diffuse hypopigmentation, background tessellation and temporal crescent being the others.
Search for a risk factor for involvement of eye in vitiligo cases shows the location of lesion to be a prime suspect. The eye is involved more in cases with vitiligo lesion located around the orbital or oral areas or in the region of patient's genitalia. The duration of vitiligo is not a contributing factor towards ocular involvement. The demographic characteristics of the patient are neither responsible for the ocular changes seen in vitiligo cases nor they act as risk factors for ocular involvement in vitiligo cases.
References
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Kovacs SO. Vitiligo. J Am Acad Dermatol. 1998;38:647-66.
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Behl PN, Kotia A, Sawal P. Vitiligo: Age related trigger factors and morphological variants. Ind J Dermatol Venereol Leprol. 1994;60:275-79.
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Nordlund JJ, Lerner AB. Vitiligo. It is important. Arch Dermatol. 1982;118:5-8.
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Biswas G, Barbhuiya JN, Biswas MC, Islam MN, Dutta S. Clinical pattern of ocular manifestations in vitiligo. J Indian Med Assoc. 2003;101:478-80.
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Bulbul BE, Baykara M, Ercan I, Tunali S, Yucel A. Vitiligo and ocular findings: a study on possible associations. J Eur Acad Dermatol Venereol. 2006;20:829-33.
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Rosenbaum J, Bunke A, Cooperman E, Gombos GM. Bilateral retinal pigment epithelium changes associated with periorbital vitiligo and seizure disorders. Ann Ophthalmol. 1979;11:1191-3.
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Albert DM, Wagoner MD, Pruett RC, Nordlund JJ, Lerner AB. Vitiligo and disorders of the retinal pigment epithelium. Br J Ophthalmol. 1983;67:153-6.
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