https://orcid.org/0000-0002-5000-3360
Abstract
Drug-induced uveitis is a rare and often under-recognised entity. We present a rare case series of bilateral anterior uveitis associated with Mediclore, a thermosensitive anti-adhesion agent composed of gelatine, chitosan, and poloxamer, used in obstetric and gynaecologic surgery. Nine female patients aged 30–51 were included; five had Caesarean sections, and four had total abdominal hysterectomy with bilateral salpingo-oophorectomy (one patient also had an appendectomy). Ocular symptoms started on the first/second postoperative day. Initial visual acuity (VA) was between 0.5 and 1.0; intraocular pressure was normal; and inflammation was mild, anterior, and frequently bilateral. Topical corticosteroids (dexamethasone, prednisolone acetate, or fluorometholone) and mydriatics were prescribed. Active infection screening was ruled out. All patients demonstrated remission with a VA of 1.0 and no persistent inflammation. Even though topical medication gave favourable results, clinicians should be aware of this potential association, ensure appropriate screening to exclude mimickers, and counsel patients accordingly.
Introduction
Uveitis refers to inflammation of the uveal tract, which includes the iris, ciliary body, and choroid. Among its many causes, drug-induced uveitis (DIU) is a rare but important and often under-recognised entity. The reported prevalence of DIU is <0.5%, though the true incidence may be underestimated due to underreporting and diagnostic challenges [1, 2]. The pathophysiology of DIU remains incompletely understood, with both direct and indirect mechanisms implicated. Direct toxicity may occur from topical, intracameral, or intravitreal administration of drugs, resulting in local tissue irritation or immune-mediated responses to drug metabolites or excipients. Indirect mechanisms include immune complex deposition in the uveal tract, immune activation from microbial antigen release, alteration of melanin’s protective function, and immune dysregulation triggered by immune checkpoint inhibitors or tumour necrosis factor (TNF)-α antagonists [1–3].
Mediclore (CGBio Co., Ltd., Seongnam, Korea) is a thermo-sensitive sol–gel anti-adhesion agent composed of biocompatible polymers, including poloxamer, gelatine, and chitosan. At room temperature, it remains in liquid form, transitioning into a gel at body temperature upon application to surgical sites [4, 5]. It is widely used to reduce postoperative adhesions and has haemostatic and antibacterial properties. Peritoneal adhesions can lead to complications such as intestinal obstruction, infertility, and chronic pelvic pain. Clinical trials have supported its safety and effectiveness in preventing adhesions in various surgical fields [6, 7].
Lim et al. [4] reported that 14 patients (0.51%) who used anti-adhesion agents received treatment for red eye and eye pain. Lim et al. [4] also stated that because chitosan is derived from crustacean shells, there is a possibility of side effects in people with crustacean allergies. Yu et al. [5] reported that diglycolic acid, a component of raw carboxymethyl chitosan and surgical anti-adhesion solutions, has antithrombogenic properties and induces vasodilation, both of which can cause conjunctival hyperaemia.
This case series describes several patients from the obstetrics and gynaecology department who developed acute anterior uveitis shortly after surgery in which Mediclore was applied. The goal of this study is to raise clinical awareness of a potential association between intraoperative anti-adhesion agents and postoperative ocular inflammation.
Case reports
This retrospective case series included patients from the Obstetrics and Gynaecology Department of a secondary general hospital in Bandung, Indonesia, who developed acute anterior uveitis following intraoperative use of an anti-adhesion agent (Mediclore) between April 2023 and March 2024. Patients were referred to the Ophthalmology Department for evaluation. Data were collected from medical records, including demographic information (age, sex), primary diagnosis, surgical procedure performed, onset of ocular symptoms (postoperative day of redness), ophthalmological examination findings (visual acuity (VA), intraocular pressure (IOP), anterior chamber (AC) cell grading), topical therapy administered, relevant laboratory investigations (including serological tests for infections: syphilis, toxoplasma, rubella, cytomegalovirus (CMV), hepatitis B/C, HIV; and routine haematology), and follow-up findings. Since the patients were still in major postoperative recovery, bedside slit lamp examinations were performed on all patients. The follow-up period was approximately one week after onset. The adverse drug reaction (ADR) Probability Scale by Naranjo et al. [8] was utilized.
A total of nine female patients were included in this case series, with a mean age of 39.2 years (range: 30–51 years). Five patients underwent Caesarean section for pregnancy-related indications, while four patients underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH/BSO) for uterine myoma; one of them also underwent appendectomy. Ocular symptoms began within 1–2 days postoperatively in all cases. All patients had anterior uveitis in both eyes; they presented with normal IOP and minimal AC inflammation (Figs 1 and 2). Initial VA ranged from 0.5 to 1.0, and inflammation was managed with topical corticosteroids (either dexamethasone, prednisolone acetate, or fluorometholone) and mydriatics (homatropine in some cases). No systemic immunosuppressive therapy was used.
Bedside examination of the eye and external inspection; (A) Case No 1; (B) Case No 2; (C) Case No 7; (D) Case No 9.
Slit lamp examination Case No. 1.
Serological screening ruled out active systemic infections such as syphilis, toxoplasma, rubella, HIV, hepatitis B/C, and CMV in all cases. Some patients showed past exposure to CMV, as indicated by CMV IgG, but no active CMV IgM was detected. At 1-week follow-up, all patients showed resolution of AC inflammation, with VA recovered to 1.0 in all cases and no persistent signs of intraocular inflammation. None of the patients had any recurrence or further complaints, as no patients attended the follow-up appointment. Details on patients’ characteristics are shown in Table 1.
Clinical features of patients
| Case no | Age | Sex | Diagnosis | Operation procedure | Onset of redness (POD) | Ophthalmology examination | Therapy (eye drops) | Laboratorium results | Follow-up (1 week) | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Visual acuity | Intraocular pressure | Anterior chamber cell | |||||||||
| 1 | 32 | F | Gravida | Caesarean section | 1 | ODS: 1.0 | N | 1 | Tobramycin, dexamethasone | Haematology routine | f/s -, VODS: 1.0 |
| 2 | 34 | F | Gravida + HIV | Caesarean section | 1 | OD:1.0, OS: 0.63 | N | 1 | Tobramycin, dexamethasone | TPHA -, toxo -, rubella -, CMV IgG reactive: 237, CMV IgM - | f/s −/−, VODS: 1.0 |
| 3 | 32 | F | Gravida + HIV | Caesarean section | 1 | ODS: 1.0 | N | 2 | Prednisolone acetate, homatropine | TPHA -, HBsAg -, toxo -, rubella -, CMV IgG reactive: 49, CMV IgM - | f/s -, VODS: 1.0 |
| 4 | 33 | F | Gravida | Caesarean section | 2 | ODS: 1.0 | N | 1 | Prednisolone acetate, homatropine | CMV IgG reactive: 43, CMV IgM -, toxo -, TPHA - | f/s -, VODS: 1.0 |
| 5 | 30 | F | Gravida | Caesarean section | 2 | OD:0.5, OS: 1.0 | N | 1 | Tobramycin, dexamethasone | TPHA -, HIV-, toxo -, rubella -, CMV IgM - | f/s −/−, VODS: 1.0 |
| 6 | 46 | F | Myoma | TAH/BSO + appendectomy | 2 | ODS: 1.0 | N | 1 | Prednisolone acetate, homatropine | HIV -, HBsAg -, HCV - | f/s -, VODS: 1.0 |
| 7 | 45 | F | Myoma | TAH/BSO | 2 | ODS: 1.0 | N | 1 | Prednisolone acetate, homatropine | Haematology routine | f/s -, VODS: 1.0 |
| 8 | 51 | F | Myoma | TAH/BSO | 1 | ODS: 1.0 | N | 1 | Prednisolone acetate, homatropine | Haematology routine | f/s -, VODS: 1.0 |
| 9 | 50 | F | Myoma | TAH/BSO | 2 | OD:0.63, OS: 0.8 | N | 1 | Fluorometholone | HIV -, HCV - | f/s −/−, VODS: 1.0 |
F, female; N, normal; OD, oculi dextra; OS, oculi sinistra; TAH/BSO, total abdominal hysterectomy with bilateral salpingo-oophorectomy; V, visual.
Discussion
DIU is a rare entity, but it can be a vision-threatening adverse event. Anti-adhesion agent-induced uveitis is a rare case of DIU [3, 9]. Based on the Naranjo et al. [8] ADR Probability Scale, the following drugs are definitely associated with uveitis: immune check point inhibitors, BRAF and MEK, TNF-α antagonists (infliximab, adalimumab, etanercept), anti-VEGF agents (ranibizumab, bevacizumab, aflibercept), cidofovir, rifabutin, sulphonamides, bisphosphonates, metipranolol, brimonidine, prostaglandin analogues, and Bacillus Calmette–Guérin (BCG) vaccine [9, 10].
Patients with uveitis require comprehensive uveitis screening, which may include serologic tests for viral, bacterial, fungal, and other infections. By obtaining a detailed history, including a thorough review of systems, physicians can identify these medications and avoid expensive, laborious, and unnecessary radiological and laboratory workup. Aqueous fluid for polymerase chain reaction for herpes simplex virus, CMV, varicella-zoster virus, and rubella should be performed if clinically indicated [9].
A well-established Naranjo Algorithm, or ADR Probability Scale, assesses whether there is a causal relationship between an adverse clinical event and a drug [8]. The Naranjo criteria are a standardised tool used to assess the probability that an adverse reaction is attributable to a specific medication. It comprises ten questions that either support or refute the likelihood of a drug-related event, generating a cumulative score that categorises the reaction as ‘definite’, ‘probable’, ‘possible’ or ‘doubtful’. This is a useful tool for evaluating a patient with a potential DIU [3, 8].
Our patients underwent laboratory testing to exclude other causes of uveitis, but there is no standardised laboratory evaluation for all patients. Our patients developed red eyes 1–2 days after surgery, and Mediclore was used as an anti-adhesive agent and after we analysed all patients using the ADR Probability Scale from the Naranjo Criteria, our patients were included in the Probable category, with a score of 6. Probable means this reaction: [1] followed a reasonable temporal sequence after a drug [2], followed a recognised response to the suspected drug [3], was confirmed by withdrawal but not by exposure to the drug, and [4] could not be reasonably explained by the known characteristics of the patient’s clinical state [3, 9].
The definitive management of a DIU usually requires cessation of the offending drug. Most cases of DIU respond promptly to discontinuation of the suspected agent in conjunction with systemic and/or topical corticosteroid and cycloplegic/mydriatic therapy. However, this must be done in consultation with the patient’s treating ophthalmologist and related physician. In these cases, Mediclore was administered only once to patients, and all patients responded to topical corticosteroid therapy [3, 10].
Subsequent ophthalmological exams may be conducted every 3–6 months to monitor for severe ocular adverse events or immediate referral to a uveitis specialist within a few days if ocular changes are reported. DIU is almost always reversible within weeks of discontinuation of the drug and treatment of the inflammation, which may be controversial in some life-prolonging therapies [9].
Mediclore (CGBio Co., Ltd., Seongnam, Korea) is a thermo-sensitive sol–gel anti-adhesion agent composed of biocompatible polymers, including poloxamer, gelatine, and chitosan. Yu et al. [5] reported that diglycolic acid, a component of raw carboxymethyl chitosan and surgical anti-adhesion solutions, has antithrombogenic properties and induces vasodilation, both of which can cause conjunctival hyperaemia [4].
A previous study reported that anti-adhesion agents containing chitosan and intraocular inflammation are thought to be related [4]. The main ingredients of the anti-adhesion agent used in this study are chitosan, poloxamer, and gelatin. Chitosan is a polysaccharide obtained through the deacetylation of chitin, a component of crustacean shells. It has anti-inflammatory, antioxidant, antibacterial, and anticancer effects and is widely used across various fields. Since chitosan is produced by processing crustacean shells, there is a potential risk of side effects in individuals with crustacean allergies. However, to date, no cases of crustacean allergy manifesting as uveitis have been reported [4].
Uveitis is the main cause of blindness and is a common ocular complication of HIV. The prevalence of uveitis in patients with HIV is 1.1%–24% [11]. Compared with HIV-negative patients, HIV-positive patients have a five-to-six-fold higher chance of being diagnosed with uveitis. Meanwhile, the depletion of CD4+ T cells induced by HIV and consequent opportunistic infections and co-infections has increased the prevalence of uveitis as an HIV-related ocular complication. The causes of uveitis in HIV infection can be divided into four main categories: HIV-induced uveitis, co-infections-related uveitis, immune recovery uveitis, and DIU [11, 12].
HIV infection most commonly leads to uveitis, including immune recovery uveitis, retinitis, or other opportunistic infection-related uveitis [12]. The most common causes of co-infection-related uveitis in HIV patients were syphilis and tuberculosis. The risk of infection increased in patients with CD4+ cell counts <50 cells/μl. HIV-related uveitis generally presents as posterior segment disease. However, DIU in patients with HIV is mostly anterior uveitis. Most DIU cases are caused by cidofovir and rifabutin, although the use of these two drugs has greatly reduced in the antiretroviral era [11].
We had two patients with HIV who underwent Caesarean section. Laboratory findings revealed no active CMV infection. Patient number 2 had CD4 absolute: 301 (normal range: 404–1621) and CD4(%): 26 (normal range: 33–58). Patient 3 did not have CD4 laboratory data. We concluded that these two patients had Mediclore-induced uveitis and excluded any other causes of uveitis from laboratory findings and history.
The strength of this study lies in its novelty, as reports of anti-adhesion agent–induced uveitis are extremely rare. This is the first case series reporting Mediclore-induced uveitis. For further study, prospective, multicentre studies are needed to estimate the incidence and identify risk factors for postoperative uveitis after anti-adhesion agents, with a longer follow-up period and detailed clinical documentation. The application of the Naranjo ADR Probability Scale provides a structured approach to causality assessment. However, the study is limited by its small sample size, a retrospective single-centre design, and a short follow-up period, which preclude evaluation of recurrence or long-term outcomes. The absence of standardised laboratory testing across all cases may also have limited the ability to exclude alternative aetiologies of uveitis completely. Furthermore, since all the patients were still in major surgery recovery, only bedside slit lamp examination was performed. Therefore, there was a lack of an AC slit lamp photo in this study.
As a conclusion, Mediclore-induced uveitis is a probable DIU. All patients had mild anterior uveitis, responded well to topical corticosteroid therapy, and fully recovered. We can give Mediclore to a patient at risk of adhesions after abdominal surgery. Still, we must inform them that there is a risk of developing mild uveitis after surgery because of the adverse event of this medication.
Conflicts of interest
None declared.
Funding
This case series did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Patient consent
Patients’ written informed consent was obtained for any case details and any accompanying images published.
