Clinical profile, optical coherence tomography, and outcomes of uveitic macular edema at a tertiary eye care center in India

Abstract

AIM:

To investigate the prevalence, optical coherence tomography (OCT) features, and visual outcomes in patients with uveitic macular edema (UME).

METHODS:

This was a retrospective, observational study conducted by a single uvea specialist at a tertiary eye care center in South. We analyzed UME cases at a tertiary eye care center between 2019 and 2024. Demographic data, OCT patterns, and edema thickness and visual acuity were analyzed.

RESULTS:

We analyzed UME cases at a tertiary eye care center between 2015 and 2019. The mean age was 42.20 ± 29.80 years. Females were more common than males (25:17). UME was found mostly in intermediate uveitis (33, 60%). Cystoid with neurosensory detachment (NSD) was the most common type (24, 42.9%), followed by the cystoid type (22, 39.3%). The mean follow-up duration was 3.75 months. UME thickness was 536.6 ± 375.8 μ before treatment, and posttreatment, it partially resolved to 372.9 ± 367 μ. After treatment, UME completely resolved in 22 (39.2%) cases, partially resolved in 24 (43.6%), remained unchanged in 6 (10.9%), and deteriorated in four (7.3%) eyes. The mean final best-corrected visual acuity was 0.41. A statistically significant difference was observed in the pre- and posttreatment visual acuity and macular edema thickness (P = 0.001).

CONCLUSION:

This study showed that UME is more common in females, occurs in middle age, and is more common in intermediate uveitis. Cystoid with NSD was the most common. Visual acuity improved with treatment in the majority of the cases. Disease-specific outcomes, investigative modalities, and treatment used are the factors influencing assessment and final visual outcome.

Introduction

Macular edema is one of the complications of several inflammatory or noninflammatory conditions with a broad spectrum of clinical entities. Uveitic macular edema (UME) is one among and forms as one of the main causes of visual morbidity in patients with both infectious and noninfectious uveitis. Uveitis is the inflammation of the uveal tract that includes the ciliary body, choroid, and iris, which is classified as per the site of inflammation into anterior, intermediate, posterior, or panuveitis according to the SUN working group of classification criteria.[1] UME is defined as the accumulation of fluid within the retinal layers as cystoid spaces in the subretinal space between the retinal pigment epithelium (RPE) and neurosensory retina, which results in the breakdown of the blood-retina barrier after the inflammation.[2] According to tertiary referral clinic reports, the UME range has varied from 20% to 30%.[3] UME with posterior uveitis, panuveitis, and intermediate uveitis are more common than anterior uveitis. Even though anterior uveitis is not common, it usually takes place in conjunction with HLA B27 with an incidence of 9%–28% of cases, Intermediate is the most common with an incidence of 20%–75%, 19%–34% of cases in posterior uveitis, and 18%–66% in panuveitis. In the case of noninfectious uveitis, macular edema occurs in 8.3% of cases.[4] Studies have shown that macular edema accounts for 35%–42% of cases of visual impairment in uveitis.[5] The exact mechanism causing extracellular fluid accumulation is unknown despite its widespread occurrence. At the same time, there is a possibility that the blood-retinal barrier and the RPE pump are compromised.[6] It may occur due to a breach in the blood-retinal barrier due to inflammation, leading to increased permeability and fluid accumulation in the intraretinal or subretinal spaces. There may also be inflammatory contracture and shrinkage of vitreous, resulting in traction over the macula. The main aim of treatment is to bring the inflammation under control, resolve the ME, and prevent its recurrence. If left untreated, severe or chronic UME could result in retinal cell damage and macular damage, resulting in permanent visual impairment.[4] Other than clinical evaluation, fundus fluorescein angiography and optical coherence tomography (OCT) were the mainstay investigations for clinically diagnosing macular edema. Earlier macular edema was assessed using a fundus fluorescein angiogram, where the leakage in the macula was looked at, but it lacked the quantifying aspect of the edema.[7] With advancements, OCT (Spectral-Domain) stands as a gold-standard diagnostic tool in aiding the diagnosis and quantitatively measuring the macular thickness, which helps in monitoring the disease progression and the prognosis after interventions.[8] Furthermore, it was reported that visual acuity is in congruence with the macular thickness rather than with the macular leakage.[8] The current approach to managing UME is by controlling the inflammation that gives rise to the macular edema. It starts with systemic oral corticosteroids such as prednisolone, immunosuppressive agents such as cyclosporine, methotrexate or azathioprine, biologics such as adalimumab, subconjunctival injection of triamcinolone acetonide, interferon-α2a (Intefen) subcutaneously, intravitreal dexamethasone (ozurdex), and intravitreal injection of fluocinolone acetonide (Yutiq).[9] While studies have been conducted on the Asian population, there is scarce data related to UME in the Indian population, hence, our study aims to investigate UME with the aid of OCT at baseline and after initiation of treatment strategies and its visual outcome at a tertiary eye care center at a tertiary eye care center in India.

Methods

The study was approved by the institutional review board and adhered to the tenets of the Declaration of Helsinki. In an observational study, patients diagnosed with UME between 2019 and 2024 were collected retrospectively at a tertiary eye care center in the Department of Uvea, Medical Research Foundation, Chennai, Tamil Nadu, India. Data included subjects who were clinically diagnosed and confirmed with OCT as macular edema, i.e. associated with uveitis. Uveitis is classified according to the SUN classification criteria of standardization of Uveitis Nomenclature as Anterior, Intermediate, Posterior, or Panuveitis. Patients who were lost to follow-up or those without OCT investigation either in the baseline visit or follow-up visit, or those with macular edema associated with any other coexisting retinal pathology such as such as retinal vein occlusion, significant visual obstruction such as significant cataract or central corneal opacity were excluded. Visual acuity for distance was noted in logMAR notation at the presentation of UME and after the treatment. Macular thickness values measured using OCT (Spectralis spectral domain-OCT, Heidelberg Engineering, Heidelberg, Germany) were noted at each follow-up until the resolution of UME. The thickness of UME was measured by a line extending from the peak of the foveal contour to the RPE. Macular edema was classified and considered as focal, diffuse, cystoid, and sensory retinal detachment. Focal macular edema is defined as an area of retinal thickening less than two-disc diameter, whereas diffuse macular edema is defined as retinal thickening with two or greater than two-disc diameter. The major difference between focal and diffuse is that diffuse macular edema involves the fovea, whereas focal does not. Cystoid macular edema is a form of macular thickening with cystic intraretinal spaces between the outer plexiform and inner nuclear layer. Sensory retinal detachment occurs when subretinal fluid (SRF) accumulates between the neurosensory retina and RPE. In our study, we included macular edema with and without the sensory retinal detachment. Various treatments were administered to the patient at presentation and throughout the follow-up duration until the resolution of UME was noted. Treatment options involved topical Nonsteroidal Anti-inflammatory Drugs (NSAIDs), systemic oral steroids, oral immunosuppressive agents, and biologics given individually or in combination as per the severity of the condition. Further treatment involved posterior triamcinolone injection, intravitreal triamcinolone acetonide, or intravitreal dexamethasone. The resolution of UME following the treatment was noted and documented as resolved, improved, maintained, or deteriorated. Visual acuity and macular thickness were noted after the initiation of the treatment until the last follow-up or till the resolution of UME.

Patients were also grouped according to their age as young (≤40 years), middle-aged (40–60 years), and elderly (≥60 years), and findings were analyzed again to see if there was any significant difference between the three groups.

Statistical analysis

Statistical significance was calculated by the Wilcoxon signed–rank test and t-test and P < 0.05 was considered statistically significant.

Results

Fifty-six eyes of 42 patients between 5 and 67 years of age were analyzed. The mean age was 42.2 ± 29.8 years. Females were more common than males (25:17). The mean best-corrected visual acuity (BCVA) was 0.58 by logMAR methodology. UME was found mostly in intermediate uveitis (33, 60%), followed by panuveitis (12, 21.4%) and posterior uveitis (10, 18.2%). One (1.82%) case of anterior uveitis also had UME. Cystoid with neurosensory detachment (NSD) was the most common type (24, 42.9%), followed by cystoid type (22, 39.3%) and diffuse type (9, 16.4%) and NSD type (1, 1.8%). The mean follow-up duration was 3.75 months. UME thickness was 536.6 ± 375.8 μ before treatment, and posttreatment, it was 372.9 ± 367 μ. After treatment, UME completely resolved in 22 (39.2%) cases, partially resolved in 24 (43.6%), remained unchanged in six (10.9%), and deteriorated in four (7.3%) eyes. The mean final BCVA was 0.41 by logMAR. Representative OCT patterns of uveitic macular edema, including diffuse macular edema, cystoid macular edema, and cystoid macular edema with neurosensory detachment, are shown in Figure 1.

Figure 1.

Structural optical coherence showing (a) Diffuse macular edema, (b) Cystoid macular edema, (c) Cystoid type of macular edema with neurosensory detachment

Thirty-six (65.5%) eyes were treated with oral steroids, 32 (57.1%) with immunosuppressant, 17 (30.9%) with topical NSAIDs, 15 (26.8%) with posterior subtenon triamcinolone acetonide injection, nine (16.1%) with intravitreal, and one (1.8%) with biologic (adalimumab) and one (1.8%) with janus kinase inhibitor. Out of the nine eyes treated with intravitreal injection, six eyes received intravitreal dexamethasone implant (Ozurdex).

The baseline characteristics of UME in the different age groups are elaborated in Table 1.

Table 1.

Characteristics of uveitic macular edema on the basis of age

Age category	≤40 years, n (%)	≤50 years, n (%)	≤60 years, n (%)
Number of patients	14	24	4
Males	5 (35.7)	11 (45.8)	1 (25)
Females	9 (64.3)	13 (54.2)	3 (75)
Eyes	21	30	5
BCVA (logMAR)
Initial	0.6	0.5	0.9
Final	0.4	0.4	0.7
UME thickness (µ)
Initial	503.9	557.4	531.4
Final	372.8	392	337.25
Pattern on OCT
Cystoid	4 (19)	14 (46.7)	3 (60)
NSD	0	1 (3.3)	0
Cystoid + NSD	11 (52.4)	12 (40)	1 (20)
Diffuse	6 (28.6)	3 (10)	1 (25)
Response to treatment
Resolved	9 (42.9)	13 (10)	1 (25)
Improved	8 (38.1)	12 (40)	3 (60)
Maintained	3 (14.3)	3 (10)	0
Deteriorated	1 (4.8)	2 (6.7)	1 (20)
Follow-up (months)	3.9	3.8	5.8

BCVA: Best-corrected visual acuity, UME: Uveitic macular edema, OCT: Optical coherence tomography, NSD: Neurosensory detachment

Significant improvement in final visual acuity was noted after treatment was initiated to bring the inflammation under control (P = 0.003). The thickness of UME was not influenced by the presenting age. The middle-aged group seems to show a higher frequency of complete resolution of UME. Delay in clearance of edema is seen in the elderly group probably due to the decreasing efficiency of physiologic phenomenon as a whole with increasing age.[10]

Discussion

UME is the leading cause of visual impairment in uveitic patients. When compared to other studies, our study showed an increased prevalence of UME.[11] It can occur due to intraocular inflammation and can persist even after the resolution of uveitis and across infectious and noninfectious types.[12] In noninfectious uveitis, UME is the most frequent complication and cause of a decrease in vision.[13] Studies in the Asian population.[9,14] showed that posterior uveitis and panuveitis are the entities most associated with UME. However, in our study, IU formed the majority of the underlying causes of UME. Another study conducted in India also revealed IU as the most frequent type of uveitis, having UME with a male preponderance.[15] In this study, female preponderance was seen across all the age groups, and the initial presenting BCVA was the worst in the elderly group (P = 0.02 with ≤ 40 years group and 0.01 with the middle-aged group.). Tungsattayathitthan et al.[16] also reported a female preponderance in the Asian population. The three primary patterns on OCT described in UME are cystoid edema, diffuse edema, and serous retinal detachment.[17] Gupta et al.[15] reported the cystoid type of UME as the most frequent, followed by the diffuse type and then the cystoid type with SRF. In this study, the cystoid type associated with NSD was seen most frequently, followed by the cystoid type and then the diffuse type. The percentage of cystoid was higher in the elderly group. Previous literature has shown an association of SRF with a more favorable visual outcome,[18] whereas Matas et al.[19] failed to find any such association. In our study, the cystoid type of UME associated with NSD had better visual outcomes than the cystoid type not associated with NSD (P = 0.03), while there was no significant difference between the presenting visual acuity. It was reported that the final visual acuity was negatively correlated with the presence of the cystoid type of UME and SRF.[20] In this study, however, the number of cases with focal and diffuse types of UME was too few to compare against the cystoid type. Initial macular edema thickness ≤ 300 μ was associated with a better final visual outcome (P = 0.01). There is a higher probability of outer retinal defect with increased thickness of macular edema, resulting in irreversible visual impairment.[21] The presence of epiretinal membrane without any retinal surface distortion had no significant effect on the final visual outcome. OCT biomarkers used in the prognosis of UME are central subfield thickness, disorganization of retinal inner layers (DRIL), and integrity of the ellipsoid zones (EZ).[22] The MUST trial suggests that a negative correlation exists between central subfield thickness and BCVA, and this is considered one of the simplest measures to assess retinal thickness in UME.[21] The integrity and reflectivity of EZ provide information on photoreceptor health, which in turn translates into a prognosis of visual improvement.[23] DRIL can interfere with the processing and relaying of visual information and can disrupt this visual signaling.[24] Thus, UME has unique structural characteristics clinically and on OCT, which can be used as an assessment tool.

Out of six eyes receiving intravitreal dexamethasone implant injection, one had ocular TB and another had ocular syphilis. Although intravitreal steroids are relatively contraindicated in infective uveitis, our study showed that they can be administered once the infection is fully under control and a good response is noted.

The structural integrity of retinal layers, investigative modality used to assess thickness, treatment, resolution, and prognosis of edema depends on the cause, activity, and severity of uveitis.[8] It has been reported that changes in retinal thickness by about 20% in patients with UME are optimal for the changes in visual acuity.[25] The presence of associated structural alterations can harm the visual prognosis.

This study had many limitations. The data were collected from a single center by a single uvea specialist, and it was a retrospective observational study. Different OCT machines were used across the years in different patients. Many patients with UME were excluded as they did not undergo OCT or did not have proper follow-up. The time frame for measuring the effect of treatment on UME also varied depending on the patient’s follow-up.

Conclusion

UME is more common in females, occurs in middle age and is more common in intermediate uveitis. Cystoid with NSD was the most common type of UME noted. Visual acuity improved with treatment in the majority of the cases. We have also emphasized that the use of an Ozurdex implant in uveitis with an infective etiology once the infection is fully under control. This study adds to the existing literature regarding clinical profile, OCT features, and outcomes in UME in the Indian population.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.