Strategies for successful management of moderate and severe Mooren’s ulcer at a rural center during the COVID-19 pandemic: Lessons learnt

Abstract

Purpose:

This study aimed to report the strategies that evolved in managing Mooren’s ulcer (MU) at a resource-limited center in rural India during the coronavirus disease 2019 (COVID-19) pandemic.

Methods:

This study includes a retrospective analysis of clinically diagnosed MU cases from January 2021 to August 2021 wherein strategies for management were developed. The demographic profile, ulcer clinical features, treatment algorithms (medical and surgical), complications encountered, referral to a higher center, and compliance with medication and follow-up were studied.

Results:

The mean age of presentation was 68.1 years (range, 62–73 years), and 90% were men. The median best-corrected visual acuity (BCVA) was 1.26 logarithm of the Minimum Angle of Resolution (LogMAR) (interquartile range (IQR), 0.00–5 logMAR) in the affected eye on presentation, which improved to 0.69 logMAR (IQR, 0.00–3 logMAR) at resolution (P = 0.442). The first-line management was conjunctival resection and tissue adhesive application (90%). 70% of cases were unilateral, 50% of cases had less than 2 clock hours of involvement, and 50% had less than 50% stromal involvement. Confounding factors included infectious keratitis (2) and corneal perforation (3). The mean duration of follow-up was 96 (1–240) days. The average follow-up visits per patient were 8.8 (1–22). 90% of cases could be managed successfully at the secondary center level with two cases needing a tertiary care referral.

Conclusion:

MU can be managed effectively by following a systemic strategy of early diagnosis, surgical therapy, and rapid institution of systemic immunosuppression in a remote location-based secondary center. The strategies developed can be a guide for ophthalmologists at remote centers managing patients or who are unable to travel to tertiary institutes.

Mooren’s ulcer (MU) is an idiopathic, immune-mediated sight-threatening disease characterized by peripheral crescent-shaped corneal ulceration and progressive stromal thinning with no scleral involvement.[1,2] Medical management includes topical and systemic corticosteroids and immunomodulators. Surgically, techniques such as cyanoacrylate adhesive (CA) and bandage contact lens (BCL) application and patch grafts have been employed.[3,4,5,6,7] Watson et al.[1] described two patterns: a smoldering course in elderly individuals and a rapidly progressive course in young patients. Early initiation of adequate immunosuppressive therapy for prolonged duration is indicated in severe disease, to avoid increased ocular morbidity and permanent visual loss.[8,9,10]

Conventionally, patients with MU are referred to higher centers owing to the complex nature of the disease. Appropriate therapy is often delayed as the diagnosis is challenging, would require a battery of serological investigations, and need to administer immunosuppressive therapy when needed. It is therefore in the patient’s best interest to seek care from large eye institutes, which may be located far from their hometowns.

The ongoing coronavirus disease 2019 (COVID-19) pandemic posed serious challenges in terms of access to elective medical care for all patients in general, especially those with complex ocular disease. Due to travel restrictions and fear of acquiring the infection, patients refrained from reaching out for health care except for absolute emergencies. During these months, a dramatic drop in patients seeking health care in tertiary and secondary centers was noted.[11] Interestingly, the secondary centers took up the challenge of taking care of these patients to some extent as the patient load increased by virtue of their proximity.[12] Furthermore, with the advent and bolstering of teleophthalmology services, the lacunae of speciality care could be partially bridged by connecting tertiary care centers to secondary and primary centers via telemedicine.[13] Therefore, patients diagnosed with MU in the pre-COVID-19 era at our secondary centers who would immediately be referred to our tertiary centers were now being managed locally due to the lack of any other option.

With this background, we undertook this study to report our experience in managing MU cases and the strategies that we devised at a resource-limited center (secondary center) in rural India during the COVID-19 pandemic.

Methods

The study was conducted in a secondary center based in a remote location in the countryside. Each secondary centre (SC) is staffed by ophthalmologists for an approximately 500,000 population located in a rural area.[14]

The strategies that evolved in the management of a total of 10 patients presenting with MU during the second wave of COVID-19 pandemic between January 2021 and August 2021 were studied. The study was approved by the Institutional Ethics Committee and adhered to the tenets of the Declaration of Helsinki.

Demographic data: Age, gender, location, distance from the center; duration of symptoms, MU characteristics, visual acuity, medical and surgical therapy, complications encountered, frequency of follow-up, and referral to a higher center were evaluated.

MU diagnosis: Clinical diagnosis of a painful, crescent-shaped, peripheral (at limbus) corneal ulcer with a gray overhanging infiltrated edges and no scleral involvement was evaluated.[15]

Severe disease: The presence of ≥ two of the following was evaluated: bilaterality, one-eyed patients, >6 clock hours of active ulceration of peripheral cornea, >50% thinning in any location, impending perforation, or presence of perforation.

Ocular examination: Detailed history and eye examination (visual acuity test, slit-lamp biomicroscopy, indirect ophthalmoscopy, and intraocular pressure measurement either digitally or by Goldman applanation tonometry) were conducted by an ophthalmologist. Slit-lamp photographs without and with the application of fluorescein stain were taken at defined visits.

Microbiology: Corneal scrapings were routinely performed in all cases by taking gentle scrapings from the edge of the maximally infiltrated area and staining with Gram’s stain and 10% potassium hydroxide wet-mount preparation before instating topical steroids. Further repeat corneal scrapings were taken when infection was suspected These slides were examined by the center ophthalmologist Raghav Preetam Peraka (RPP) to rule out bacteria and fungi.

Strategies for management: All cases were discussed with an experienced cornea specialist at the centre of excellence (COE) who was actively involved in comanaging these cases, and the images were shared on a weekly basis. Management decisions were taken jointly by the local ophthalmologist and the remotely located specialist.

Medical management: The step ladder approach has been used in the conventional management of MU in tertiary center with decent success.[16] The basic principle behind the approach is to gradually step up immunosuppression starting with topical steroids and topping up with oral steroids, oral immunomodulator therapy (IMT), or intravenous methylprednisolone based on the disease laterality, severity, recurrence, and complications. The modifications from the stepladder approach[16] were made as per the challenges of remote location and extraordinary situations of COVID-19 pandemic.

1. All patients underwent were referred for baseline systemic screening to a local physician who is based 20 km away from the secondary center in a nearby village and whose help was sought to comanage the patients, to rule out any overt systemic disease or infections before initiating oral steroid and immunomodulator therapy. Serological workup: Complete blood picture (CBC), erythrocyte sedimentation rate, random blood sugar, renal and liver renal function (LFT) tests, and rheumatoid factor were obtained before the commencement of therapy. Further autoimmune work could not be performed due to limitations in travel and connectivity

2. The threshold to start on oral steroids was lower compared with the step ladder approach as patients could not follow up frequently and we could not risk worsening of the disease. Oral prednisolone 1 mg/kg was started in all cases with bilateral involvement, >6 clock hours of corneal involvement, and < 6 clock hours but > 50% stromal thinning. Before starting oral steroids, patients were counseled regarding the side effects and blood sugar levels were monitored. Corticosteroids were stepped down every week or biweekly, or earlier in case of intolerance or side effects. Oral methotrexate 7.5–12.5 mg/week was added for the following indications: a) steroid-sparing immunomodulator in cases that required prolonged (>3 months) therapy, b) additional immunosuppression in worsening disease, c) severe disease at presentation, and d) recurrent disease.

3. Intravenous methylprednisolone was given in severe cases from a local hospital as and when required.

Surgical management:

1. Conjunctival resection and CA+BCL application were performed locally as described previously.[4]

2. In case of progression of the disease on follow-up, repeat CA + BCL was performed.

Follow-up management: Resolution was defined as non-progression of the ulcer and healing with pannus or epithelization (as identified by the absence of fluorescein staining on slit-lamp examination). Once the disease showed signs of resolution, the topical steroids were tapered to a once-a-day dosage and continued for at least 3 months and oral steroids were tapered and stopped. Oral methotrexate was continued, and CBC and LFT were repeated every 2 months till 6 to 12 months beyond resolution. Recurrence was defined as an increase in symptoms and progression of the ulcer along the leading edges.

Follow-up schedules were tailor-made for individual patients based on the severity of disease and feasibility of travel for the patient. Difficulty in follow-up refers to patients who faced challenges with respect to travel to the center. Lost to follow-up refers to patients who could not further follow-up at the center despite being advised for the same.

Statistical analysis was performed on Microsoft^® Excel 2022 (Version 16, Microsoft Corporation, India). Data with normal distribution were described in terms of mean ± standard deviation and those with non-normal distribution in median and interquartile range (IQR).

Results

During the time period, the center saw 10605 new patients, of whom 10 had MU, bringing the incidence to 94.3 per 100,000.

Demographic data: The mean age was 68.1 years (range, 62–73 years). There were nine male (90%) and one female (10%) patients. The right eye was involved in three patients (30%), left eye in four (40%), and bilateral involvement in three patients (30%). The median distance from the respective villages to center was 83 kilometers (km) (15–135 km). The mean duration of follow-up was 96 days (range 1–240 days). The average follow-up visits per patient were 8.8 (1–22). Difficulty in follow-up was encountered in eight patients (80%), and one case was lost to follow-up. Table 1 lists the demographic details.

Table 1.

Demographic data

Category	Subcategory	Values
Age	Mean	68.1 years
	Median	67 years
	Range	62–73 years
Gender	Male	9
	Female	1
Laterality	Right	3
	Left	4
	Both	3
Distance to center	Mean	69 KM
	Median	83 KM
	Range	15–135 KM
	Difficulty to follow-up	8
	Lost to follow-up	1

Clinical characteristics: All presented with pain, redness, and blurring of vision in the affected eye. The median duration of symptoms was 30 (IQR: 3–120) days. In addition, two patients had a history of trauma with stick. One was treated locally for microbial keratitis and two had undergone CA and BCL application elsewhere before presentation. Four of 10 had undergone cataract surgery elsewhere. Three patients were using topical steroids before the presentation.

Visual acuity: The median best-corrected visual acuity (BCVA) was 1.26 logMAR (IQR, 0.00–5 logMAR) in the affected eye on presentation, which improved to 0.69 logMAR (IQR, 0.00–3 logMAR) at resolution (P = 0.442). Table 2 lists the clinical characteristics and visual acuities.

Table 2.

Clinical characteristics and visual acuities

Category	Subcategory	Frequency
Vision (in logMAR)	At presentation
	<1	7
	1–1.6	0
	>1.6	3
	Last follow-up
	<1	9
	1–1.6	1
	>1.6	0
Duration of symptoms (days)
	<3	0
	3–10	2
	10–30	3
	30–120	1
	>120	2
Duration to quiescence (days)
	<10	3
	11 30	3
	30–60	2
	61–120	1
	>120	0
Previous history of
	Trauma	2
	Infection	1
	Cataract surgery	4
	Therapy with steroids	3

Ulcer characteristics: On presentation, five of 10 had corneal stromal ulceration of >50% of the corneal thickness; of which, four of five presented with corneal perforation. Five of ten had >3 clock hours of corneal involvement in the periphery, and two of these five had progression to the central cornea.

Management: All the patients received topical steroids, oral steroids were started in eight of 10 (80%), intravenous methylprednisolone in two of 10, and methotrexate in four of 10 (40%) patients. Eight of ten (80%) underwent conjunctival resection and CA and BCL application. In addition, two patients, where the infiltrate was persistent with corneal melting and CA and BCL were lost, underwent additional superficial keratectomy and repeat CA and BCL application. The mean duration for achieving quiescence was 76 days (IQR: 10–300 days). Disease progression was noted in four (40%) patients, of whom one developed the disease in the other eye during follow-up, two had a relapse on stopping oral steroids and were started on oral methotrexate, and one required a tertiary center referral for intravenous therapy (after which he followed up at our center). Three patients missed their follow-up visits due to the lockdown, and one patient was lost to follow-up.

Complications: On follow-up, one patient had a fall of total leukocyte count and hemoglobin levels on hemogram following which methotrexate was stopped and the deranged parameters reversed. Three patients developed infectious keratitis on therapy of which one patient had to be referred to a tertiary center owing to malignant progression of the primary disease secondary to infection. The remaining two patients were successfully managed by stopping topical steroids, instituting appropriate antimicrobial therapy, and continuing oral immunosuppression.

Table 3 summarizes ulcer characteristics and medical and surgical management.

Table 3.

Ulcer characteristics and medical and surgical management

Category	Subcategory	Frequency
Stromal thinning	<50%	5
	>50%	5
Corneal involvement (in clock hours)	>3	5
	<3	5
	Perforation at presentation	4
Treatment
Surgical	Conjunctival resection + CA + BCL	8
	Additional superficial keratectomy	2
Medical	Topical steroids	10
	Oral steroids	8
	Methotrexate	4
	IVMP	2

CA: cyanoacrylate adhesive; BCL: bandage contact lens; IVMP: intravenous methylprednisolone

Representative case

Case 1

A 70-year-old man presented to a secondary center in January 2021 with complaints of pain, redness, and tearing in his right eye for 2 months. He had undergone CA and BCL elsewhere and was on topical steroids. Examination showed that visual acuity was counting finger close to face; the cornea showed CA in situ along the temporal peripheral margin and active infiltration at the edges from 4 to 5 o’clock nasally [Fig. 1a]. The anterior chamber was shallower temporally, and a senile cataract was noted. He was diagnosed with severe MU. He underwent conjunctival resection and repeat CA and BCL application and was started on topical and oral corticosteroids in the secondary center. He was lost to follow-up for four weeks, following which worsening of the infiltrate with edema and cellularity involving the visual axis was noted [Fig. 1b]. He was referred to a tertiary center, but was unable to travel. The plan was discussed with a local physician, and after clearance, oral steroids and methotrexate (7.5 mg/week, later stepped up to 10 mg) were started along with topical corticosteroids. A week later, a yellowish-white infiltrate [Fig. 1c] was noted. Microbial keratitis was confirmed by noting gram-positive cocci in the corneal scrapings. Fortified vancomycin 5% and ciprofloxacin 0.3% eye drops were started hourly, and topical steroids were withheld. The infection resolved [Fig. 1d] over the next 2 weeks; however, the underlying MU flared up. As travel restrictions were temporarily relaxed, he was referred to the tertiary center where he received intravenous methylprednisolone (IVMP) 500 mg, methotrexate was stepped up to 15 mg/week, and topical antibiotics could be discontinued. Subsequently, superficial keratectomy and repeat CA and BCL application were performed at the center [Fig. 2a]. The resolution was achieved over the next 10 weeks [Fig. 2b and c]. Cataract surgery was performed 3 months later, and his vision improved to 20/40 [Fig. 2d]. At the end of the one-year follow-up, the patient is maintaining a visual acuity of 20/40 and had no clinical activity and is being continued on oral methotrexate 15 mg/week and once-a-day dose of topical steroids.

Figure 1.

Standard slit-lamp photograph of the right eye. (a) On presentation, CA and BCL are in situ and active infiltration at the edges from 4 to 5 o’clock nasally. (b) At 4 weeks, worsening of infiltrate was noted. (c) At 5 weeks, yellowish-white infiltrate adjacent to the leading edge and hypopyon was noted. (d) At 7 weeks, the resolution of infection and worsening of infiltrate along the leading edge and central spread were noted

Figure 2.

Standard slit-lamp photograph of the right eye (a) At 9 weeks, consolidation of infiltrate was noted. (b) At 12 weeks, the resolution of edema and cellularity is the leading edge. (c) At 16 weeks, complete resolution of infiltrate was noted. (d) At 7 months from presentation, temporal scarring with vascularization and pseudophakia was noted

Discussion

The COVID-19 pandemic affected all routine ophthalmic practices in multiple ways.[17]

In our study, all patients were from within 150 km radius from the center. While there are a few larger towns in the proximity of 150 kms, the ophthalmologists available are mostly individual practitioners, most of whom were not seeing patients during the active part of the pandemic. Therefore, the secondary center ended up seeing and treating complex cases, which otherwise were promptly referred to the tertiary level centers in the past.

MU is rare, and the incidence rate varies based on the geographical location.[18,19] The incidence was reported to be 0.03% in a series from China,[19] which is similar to the Indian scenario as well.[20] In our study, the incidence rate is 0.094% in our hospital. This may seem a small number; nonetheless, it is a burden at the center, which is equipped to handle predominantly cataract and refractive errors and other simpler cases.

In our cohort too, we noted that the demographic profile of patients, pattern of ulceration, laterality, and complications such as perforations in our study were similar to previous studies.[16,18,19,21] Unilateral involvement was slightly more common overall contrasting with the study by Ashar et al.[16] where bilateral presentation was more common. This may be due to tertiary center bias where bilateral cases are more likely to seek attention earlier. 50% of patients presented after having symptoms for more than 30 days, suggesting the difficulties posed by the ongoing pandemic in reaching out for medical care. Four cases had difficulty in following up despite the proximity of the center and had missed appointments, two among them had stopped medications due to unavailability, which finally led to a protracted course of disease for greater than 120 days. The mean number of follow-up visits was nine visits to the center (as compared to a cataract patient who needs two or three visits) with 22 visits in one patient, which explains the chronic and protracted nature of disease and the need for continued and prolonged monitoring and management.

The BCVA at presentation was better than 20/200 in 67% of the eyes, and three patients had vision worse or equal to 20/2000. At quiescence, 73% of eyes achieved BCVA better than 20/80, and only one patient remained to have vision worse than 20/2000 due to significant corneal scarring involving the visual axis. Sharma et al.[20] have shown significant improvement in vision in severe cases, which parallels the outcomes seen in our study.

The benefits of conjunctival resection in MU, which was performed in 90% of our cases, have been well described in the literature;[3,4] however, this therapy alone is not sufficient. Immune dysregulation of unknown etiology and a high chance of recurrence necessitate the need for immunosuppression.[2,8,16] Traditionally, topical and oral steroids are used as first-line drugs as they suppress the dendritic cells and arrest the ongoing inflammatory cascade.[6,22] In our cohort, 80% of patients required oral steroids, among which 50% showed resolution following which oral steroids were tapered and stopped. Of the four patients requiring additional methotrexate, three had perforation at presentation (severe disease) and one other had a recurrence on stopping therapy. The overall threshold for using systemic immunosuppression was lower owing to the delayed presentation, disease severity, and longer intervals between follow-up visits. Overall, we noted that under supervision, even at a rural center it was possible to safely administer corticosteroids and immunomodulators under careful supervision.

This study has some limitations, which include the retrospective nature, small sample size, and absence of robust detailed serological investigations to rule out systemic autoimmune diseases (which was not possible). However, owing to the relative rarity of the disease and the extraordinary situations of pandemic, this case series provides useful insights into managing MU in a low-resource setup. The lessons learnt and the strategies we could put in place while managing these cases were as follows:

1. It is not always possible to access the best care for our patients. In all of our cases, our center was the only available eye care facility and therefore the best facility available to them.

2. While the resources may be limited in the physical sense, technology fills the gaps and much can be achieved by reviewing the cases and images with experts located at higher centers. Therefore, the first strategy is to connect with large medical hospitals where expertise is available and seek advice when in doubt.

3. Conjunctival resection and BCL application are basic surgical procedures, which can be easily performed by ophthalmologists, and the strategy should include this at an early stage.

4. Starting oral medications, especially steroids and immunosuppressants, are something that every ophthalmologist would balk at, as using these agents is not part of our routine medical therapy and most ophthalmologists are unfamiliar with administering them. Again, the strategy that we evolved was to partner with a committed local physician, to perform basic evaluations for all our patients before embarking on these medications. Expert opinion on dose, when to start or taper or stop, was taken frequently during the course.

5. The critical difference that the early institution of oral immunosuppression (both corticosteroids and immunomodulators) could make is highlighted by the results, as we could achieve disease remission and reasonably good visual outcomes in the majority of our cases, results that are comparable to published results of patients treated at apex institutions.

6. Following up this, small but critical set of patients over a difficult period and achieving success comparable to data published from major centers were extremely satisfying and heartening.

Conclusion

In summary, patients with MU were referred to a tertiary care centers in the past and were never managed at the primary level. However, the pandemic forced the patients to be managed at the rural center, more out of necessity than design. As a result of this, we could treat and demonstrate our outcomes in a resource-depleted setting using the available local resources in conjunction with telemedicine services in the hour of pandemic, which posed unique challenges with respect to a lack of transportation and a lack of availability of super-speciality services. Our strategies are encouraging in terms of successfully managing moderate and severe MU with simple surgical management (CR + TA) and adequate immunosuppression (in collaboration with the local physician), which led to excellent disease control. As the uncertainty of the ongoing pandemic continues to haunt us, ophthalmologists from the community can play a vital role in managing even difficult cases such as these.

Ethics statement

1. This study adhered to the tenets of the Declaration of Helsinki and was approved by the Institute Ethics Committee.

2. The Ethics Reference Number is LEC-BHR-R-08-22-929.

3. Written informed consent was obtained from all the patients in this study.

Financial support and sponsorship:

This study was supported by the Hyderabad Eye Institute and Hyderabad Eye Research Foundation, Hyderabad, India.

Conflicts of interest:

There are no conflicts of interest.