Clinical profile, treatment, and visual outcome of scleritis: A single ophthalmologist experience.

PURPOSE: The purpose of this study was to analyze the clinical profile of patients with scleritis managed by a single ophthalmologist in a tertiary eye care center.
METHODS: This was a retrospective analysis of 107 eyes of 96 patients with scleritis from January 2007 to December 2018.
RESULTS: Female predominance (68%) with a relatively young-onset (46 ± 14 years) of scleritis was observed. Diffuse anterior scleritis (41%) was the most common subtype of scleritis, and the most common systemic association was rheumatoid arthritis (18%). Three-fourth of patients received immunosuppressive treatment (74%) along with corticosteroids. The mean follow-up period was 3 ± 2.5 (range: 0.6-10) years. Necrotizing scleritis was at a 3.5 times higher risk of developing ocular complications. Eighty percent of patients maintained the same vision. Recurrence of scleritis was noted in 25 eyes (23%).
CONCLUSION: Diffuse scleritis is the most common scleritis in our population. Tuberculosis was commonly seen with diffuse scleritis. The likelihood of developing ocular complications (cataract and glaucoma) was higher in necrotizing scleritis, thus requiring periodic monitorization. Copyright:

Introduction

Scleritis is a painful inflammation of the outer coat of the eyeball. Depending on the anatomical location of scleral inflammation, scleritis is broadly divided into anterior and posterior scleritis.[123] Scleritis can occur due to various noninfectious and infectious causes. Patients with scleritis can develop various sight-threatening ocular complications even after anti-inflammatory therapy.[45] The majority of the literature on scleritis is from tertiary eye care centers, and often, the management of these patients involves more than one ophthalmologist.[67] We conducted a retrospective analysis of scleritis patients managed by a single ophthalmologist to know the clinical profile, treatment, and visual outcome.

Materials and Methods

The index study was a retrospective case analysis of the patients with scleritis managed by a single ophthalmologist (JB) in a tertiary eye care center from January 2007 to December 2018. The study was approved by the institutional review board of our hospital and adhered to the tenets of the Declaration of Helsinki.

Patients with scleritis having a minimum follow-up of 6 months were included in this study. Patients with other causes of red eye, prior history of trauma or ocular surgery, cases of surgically induced necrotizing scleritis were excluded. The study also excluded infective scleritis where the presence of microorganisms was confirmed with tissue diagnosis as these patients are usually managed in the cornea and ocular surface clinic of the institute. However, the study included patients with presumed ocular tuberculosis who had scleritis. The diagnosis of scleritis was made based on the clinical picture of painful inflammation of the sclera, evidence of scleral nodule, and congestion of deep and superficial scleral vessels that remained even after instillation of 10% of phenylephrine. Patients were further categorized as per Watson and Hayreh's classification into the following subtypes – diffuse, nodular necrotizing, and posterior scleritis.[3] The diagnosis of posterior scleritis was based on dilated fundus examination of the posterior segment and supported by posterior scleral thickening and “T” sign in ultrasonography.

A detailed ocular and systemic history was obtained from all the patients, and a history of joint pain, joint swelling, and contact with tuberculosis was assessed in all cases. A complete ophthalmic evaluation includes assessing best-corrected visual acuity, slit-lamp biomicroscopy, and a dilated fundus examination with + 90D/+78D and indirect ophthalmoscopy was carried out. Laboratory investigations included routine hemogram, erythrocyte sedimentation rate, antinuclear antibodies, antinuclear cytoplasmic antibodies, serum rheumatoid factor, Mantoux test, QuantiFERON-TB Gold test, high-resolution computed tomography of the chest, serum angiotensin-converting enzyme, human leukocyte antigen B-27, venereal disease research laboratory disease, and Treponema pallidum hemagglutination test. All patients were evaluated by an in-house physician and consultation from the rheumatologist and to rule out the presence of any associated collagen disease (rheumatologic, collagen vascular, or evidence of tuberculosis). Demographic details, including medical history, clinical and laboratory findings, ultrasonographic findings, management, and the visual outcome, were retrieved from the medical records.

Topical and oral corticosteroids were used as a first-line treatment in patients with diffuse anterior scleritis and nodular scleritis. Immunosuppressive agents with systemic corticosteroids were considered as first-line agents in the management of necrotizing scleritis. Posterior scleritis was treated mainly with oral corticosteroid; in case of exudative retinal detachment, optic nerve involvement pulse corticosteroid was administered. Immunosuppressive agents were also prescribed in recalcitrant cases of anterior and posterior scleritis. In patients with progressive scleral thinning, and severe scleral inflammation not responding to any of the oral medications, pulse corticosteroid was considered. These drugs were tapered and discontinued based on the clinical improvement of scleritis. Antitubercular treatment was prescribed under the guidance of a pulmonologist in cases with evidence of systemic TB.

Visual acuity was tested with a Snellen chart and converted to log MAR values. Visual outcome was defined as “improved” if there is a change in visual acuity of more than or equal to two lines at their final follow-up, “worsened” if there is a deterioration of more than two lines, and “stable” if final visual acuity remains unchanged. Further, we grouped our patients based on the presence or absence of the underlying association as an idiopathic or systemic (infectious and noninfectious) disease to look for any potential risk factors. All the parameters included in this study were analyzed using SPSS (Statistical Package for Social Sciences, Version 20.0, Chicago, IL, USA) and Microsoft Excel. P < 0.05 was considered to be significant in all the analyses.

Results

The index study includes 107 eyes of 96 patients with scleritis. The demographic details of the patients are listed in Table 1. A female (68%) preponderance was noted with a mean age at presentation 46 ± 14 (14–85) years. Majority of the patients (89%) had unilateral involvement. Ocular pain and redness (n = 93, 97%) were the most common presentation. Anterior chamber reaction was observed in 15 (14%) eyes. The retinal finding included mass-like lesion (n = 1 eye, 1%), choroidal folds (n = 2 eyes, 2%), and exudative retinal detachment (n = 1 eye, 1%). A systemic association was found in 46 (48%) patients. Of these patients, 30 (31%) patients had noninfectious etiology, and 16 (17%) patients had presumed tuberculosis.

Table 1

Clinical profile of scleritis in a tertiary care center of South India

Clinical characteristics	Results
Total number of patients	96
Total number of eyes	107
Age (year)
Mean±SD (range)	46±14 (14-85)
Mean follow-up±SD (year)	3±2.5
Gender (%)
Male	31 (32)
Female	65 (68)
Laterality (%)
Unilateral	85 (89)
Bilateral	11 (11)
Visual acuity
Presenting visual acuity
Mean±SD	0.20±0.45
Final visual acuity
Mean±SD	0.23±0.65
Type of scleritis (eyes) (%)
Diffuse scleritis	44 (41)
Necrotizing scleritis	22 (20)
Nodular scleritis	34 (32)
Posterior scleritis	7 (7)
Anterior chamber involvement (eyes) (%)
AC reaction	15 (14)
Scleral necrosis	25 (23)
Scleral nodule	26 (24)
Deeper congestion	66 (62)
Corneal involvement	10 (9)
Vitritis	7 (7)
Retina (%)
Scleral mass	1 (1)
Choroidal folds	2 (2)
Subretinal fluid	1 (1)
Retinal detachment	1 (1)
Systemic association (%)
Cogan’s disease	1 (1)
Relapsing polychondritis	1 (1)
IgG4 disease	1 (1)
Collagen vascular disease	4 (4)
Granulomatosis with polyangiitis	6 (6)
Rheumatoid arthritis	17 (18)
Tuberculosis	16 (17)
Idiopathic	50 (52)
Recurrence (%)	25 (23)

SD: Standard deviation

All patients (100%) required oral corticosteroid therapy at a dose of 1 mg/kg/day in a tapering schedule. Intravenous pulse steroid therapy was administered in six (6%) patients, and anterior subtenon injections were given in 18 (19%) eyes initially to have a rapid, efficient control of the intensive inflammation and were shifted to oral corticosteroids subsequently. Seventy-one (74%) patients had immunosuppressive therapy; the majority of patients were treated with mycophenolate mofetil (54%) and cyclophosphamide (27%). One (1%) patient received a rituximab injection. Side effects including increased blood pressure, blood sugar level, and abnormal kidney/liver function were noted in four patients (4%) of the population.

The mean follow-up period was 3 ± 2.5 (range: 0.6–10) years. The average visual acuity at presentation was 0.20 ± 0.45 logMAR units and at the final visit was 0.23 ± 0.65 logMAR units. Twenty-five eyes (23%) had a recurrence during the follow-up period [Table 1]. Thirty-five eyes (33%) developed a complicated cataract and required surgical intervention. Twenty-one eyes (20) developed ocular hypertension and were managed by antiglaucoma medications except one that required surgical intervention. Two eyes (9%) with necrotizing scleritis eventually developed globe perforation and required patch graft. Thirteen (26%) patients developed more than one complication. Regarding visual outcome, 9 of 107 eyes (8%) worsened, stable in 86 (80%) eyes, and improved in 12 (11%) eyes [Table 2].

Table 2

Treatment modality, complications, and visual outcomes of the patients with scleritis

Treatment (patients, %)		Complications (eyes, %)		Visual outcome (eyes, %)
Nonsteroidal anti-inflammatory drugs	6 (6)	Cataract	35 (33)	Worsened	9 (8)
Topical steroids	8 (8)	Glaucoma	21 (20)	Stable	86 (80)
Systemic corticosteroids	96 (100)	Cystoid macular edema	4 (4)	Improved	12 (11)
Intravitreal methyl prednisolone	6 (6)	Uveitis	10 (9)
Anterior sub tenon injection	18 (19)	Corneal involvement	3 (3)
Combined therapy (oral corticosteroid + IMT)	71 (74)	Perforation	1 (1)
Cyclosporine	2 (3)
Azathioprine	3 (4)
Methotrexate	9 (13)
Cyclophosphamide	19 (27)
Mycophenolate mofetil	38 (54)

IMT: Immunomodulatory therapy

For analysis purposes, we classified our population based on the presence of underlying disease (excluding patients of presumed scleritis). The mean age at presentation in the idiopathic group was 44 ± 13 years (range: 16–68), and in the systemic disease group, it was 46 ± 17 years (range: 11–85). Female preponderance was seen in both the groups (idiopathic: 34, 69% and systemic disease: 15, 48%). The demographic details of the systemic and idiopathic groups are listed in Table 3. Regarding visual outcome, no statistically significant difference was noted between these groups (P > 0.05). Although there was no difference in the rate of recurrence (P > 0.05) between these groups, the rate of complication (P < 0.05) was significantly higher in patients associated with systemic disease.

Table 3

Demographics of scleritis with and without systemic disease association

	Systemic scleritis group	Idiopathic scleritis group
Total number of patients	31	49
Total number of eyes	37	54
Age	46±17 (11-85)	44±13 (16-68)
Gender
Male:female	10:15	21:34
Visual acuity
At presentation	0.35±0.60	0.13±0.29
At final follow-up	0.43±0.88	0.12±0.28
Type of scleritis (eyes, %)
Diffuse scleritis	17 (46)	19 (35)
Nodular scleritis	9 (24)	18 (33)
Necrotizing scleritis	9 (24)	12 (22)
Posterior scleritis	2 (5)	5 (9)
Complications (eyes, %)	21 (57)	19 (35)
Recurrence (eyes, %)	7 (19)	22)

Further, the parameters such as the visual outcome, number of recurrences, and the rate of complications were analyzed with the type of scleritis. The details are given in Table 4. We found no statistically significant difference in the visual outcome and the recurrence rate between these categories (P > 0.05). The necrotizing scleritis had a higher rate of complications than other types of scleritis (P < 0.05). Logistics regression was performed to calculate the risk factors for developing complications. It was found that patients who had necrotizing scleritis are 3.5 times higher at risk of developing complications than other scleritis (P < 0.05, 95% confidence interval: 1.12-11). In our study, age, gender, and laterality were not found to be a good predictor for calculating the risk factor of developing complications (P > 0.05).

Table 4

Clinical characteristics of subtypes of scleritis

Type of scleritis	Diffuse scleritis (%)	Nodular scleritis (%)	Necrotizing scleritis (%)	Posterior scleritis (%)
Total number of patients	39	32	20	5
Total number of eyes	44	34	22	7
Gender
Male	12 (31)	9 (28)	9 (45)	1 (20)
Female	27 (69)	23 (72)	11 (55)	4 (80)
Laterality
Unilateral	34 (87)	30 (94)	18 (90)	3 (60)
Bilateral	5 (13)	2 (6)	2 (10)	2 (40)
Systemic association
Cogan’s disease	1 (3)	0	0	0
Relapsing polychondritis	0	1 (3)	0	0
IgG4 disease	1 (3)	0	0	0
Collagen vascular disease	2 (5)	0	2 (10)	0
Granulomatosis with polyangiitis	2 (5)	1 (3)	3 (15)	0
Rheumatoid arthritis	7 (18)	6 (19)	3 (15)	1 (20)
Tuberculosis	8 (21)	7 (22)	1 (5)	0
Idiopathic	18 (46)	18 (53)	11 (55)	4 (80)
Treatment
Nonsteroidal anti-inflammatory drug	3 (8)	2 (6)	0	1 (20)
Topical steroids	5 (13)	2 (6)	1 (5)	0
Systemic corticosteroids	39 (100)	32 (100)	20 (100)	5 (100)
Intravitreal methyl prednisolone	1 (3)	2 (6)	2 (10)	1 (20)
Combined therapy (oral corticosteroid + IMT)	31 (79)	22 (69)	15 (75)	3 (60)
Cyclosporine	0	0	2 (13)	0
Azathioprine	0	1 (5)	1 (7)	1 (20)
Methotrexate	5 (16)	3 (14)	0	1 (20)
Cyclophosphamide	6 (19)	5 (23)	8 (53)	0
Mycophenolate mofetil	20 (65)	13 (59)	4 (27)	1 (20)
Patch graft	0	0	2 (9)	0

IMT: Immunomodulatory therapy

Discussion

The index study provides the clinical characterization of scleritis based on the data of 96 cases from the clinic of single uveitis and ocular inflammatory disease expert. The demographics of our study were found to be similar to previously reported studies, having a female preponderance and unilateral involvement.[89] It was evidenced that the bilateral involvement of scleritis is more associated with active systemic disease.[10] The lower rate of systemic involvement (48%) found in our series may be a possible reason for the higher rate of unilateral involvement. The overall age at onset in our study population (46 ± 14 years) is slightly younger than the studies from other parts of the world with the other studies done in India.[59] Also, our finding confirms scleritis in India affects relatively younger population than other parts of the world.[11121314151617181920] Relatively younger age at presentation (37 ± 21 years) was noted in patients with posterior scleritis. Most importantly, four out of five patients with scleritis were <50 years.

Diffuse anterior scleritis was the most common scleritis type in our study, followed by nodular scleritis in our cohort. This frequency and subtypes were inconsistent with the studies in the literature.[141516] The present study showed that 31% of scleritis from India had a systemic autoimmune disease. This finding is similar to previously published studies.[521] Only systemic infectious disease associated with scleritis in our subset of patients was TB. The reported prevalence of TB in our patients was in accordance with the other studies.[822] TB was found to be more commonly associated with diffuse anterior scleritis than with any other forms. In contrast, studies from Bangladesh and India revealed a significant association of mycobacterium tuberculosis in patients with nodular scleritis.[15] Considering the high prevalence of TB in India, it is recommended to screen all patients with scleritis for TB irrespective of clinical subtype. Mccluskey et al.,[23] in their study of 99 patients with posterior scleritis, found 29% of patients to have associated systemic disease and recommended aggressive treatment with immunosuppressive agents. Similarly, we found one out of five patients (20%) with posterior scleritis to have a systemic association.

In our series, 44% of the patients had scleritis-associated ocular complications. Of all subtypes, necrotizing scleritis is found to be associated with a higher complication rate. Necrotizing scleritis is a severe and destructive form of scleritis associated with multiple ocular complications that can lead to severe vision loss. The regression model developed in our study showed 3.5 times higher risk of developing ocular complications in necrotizing scleritis than other types of scleritis. However, the ocular complication was not found to have any association with age, gender, laterality, and the presence of systemic disease. In our study, the development of cataracts was the major ocular complication, which can be attributed to the frequent use of systemic corticosteroids. Besides, the presence of anterior uveitis in scleritis warrants the usage of topical steroids, thereby increasing the risk of developing raised intraocular pressure. In our population, the presence of anterior uveitis was noted in 14%. In a study by Yang et al.,[17] anterior uveitis was reported in 9% of scleritis eyes and one of the major complications.

Systemic corticosteroids were used as a first-line treatment in our study. Almost, three quarter of the study cohort required a combination of systemic steroids with immunomodulatory treatment. By far, the most frequently used agent was mycophenolate mofetil (54%). Studies have proved its efficacy in controlling inflammation prolonged period with minimal adverse effects and patient's tolerability.[2425] The other immunomodulators used in our study were cyclophosphamide, methotrexate, azathioprine, and cyclosporine at a decreasing rate. In our cohort, a worsening of visual acuity was observed only in 8% of the patients. This is much less as compared to other studies.[1523] Use of immunosuppressive agents might have helped in maintaining or improving the vision of the remaining 92% of the patient in our study. Two patients with necrotizing scleritis in our series developed globe perforation despite all treatment and including biologics given in one patient. This can be explained by a late presentation with severe inflammation and poor compliance. We suggest all scleritis patients to follow-up at regular intervals to avoid any serious ocular complications.

In our study, the majority of the patients were treated with oral corticosteroids (99%). However, immunosuppressive agents used in our population are relatively higher when compared with other studies. This could be, however, attributed to being a tertiary referral eye care center, managing the difficult, recalcitrant, and aggressive disease. The reduced recurrence rate in our study is similar to other studies and is partly attributed to the higher use of immunosuppressives.[1415]

As a retrospective study, it has its limitations. It may also be biased because of the referral of severe cases to our tertiary center and may not represent the actual disease spectrum in the Indian population. A prospective, randomized study with a uniform study group is required to analyze the actual profile of such patients. However, these data may provide some understanding of the disease profile in a cohort of patients seen by a single uveitis expert.

Conclusion

Our study provided clinical patterns and treatment outcomes of scleritis among the Indian population by a single uveitis expert. Diffuse scleritis is frequently found and common among tuberculosis and rheumatoid arthritis patients. Combination of systemic corticosteroids and immunosuppressive treatment effectively controlled scleritis with better clinical and visual prognosis. In addition, from our study, we found necrotizing scleritis to be associated with developing complications. We highly recommend periodic eye examination in these patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.