Authors: Efthymia Kalogera, Evangelos Spanos, Michael Karampelas, Ioannis Halkiadakis, Vasileios Peponis, Kallirroi Konstantopoulou
Categories: Case Series, BADI, BAIT, COVID-19, Greece, Iris, Moxifloxacin, Transillumination
Source: Ophthalmology and Therapy
Authors: Efthymia Kalogera, Evangelos Spanos, Michael Karampelas, Ioannis Halkiadakis, Vasileios Peponis, Kallirroi Konstantopoulou
Bilateral acute iris transillumination (BAIT) is a recently described entity, usually following moxifloxacin intake or respiratory tract infections. Interest in the disease has increased since the COVID-19 pandemic; however, its etiopathogenesis remains unclear. This study presents five cases in Greece with symptoms and signs suggestive of BAIT after systemic moxifloxacin administration. Unusual clinical manifestations and differential diagnosis are highlighted.
Five female patients presented to the Uveitis Department complaining of bilateral photophobia and redness following systemic moxifloxacin intake. Past ocular history was unremarkable. The median best corrected visual acuity (BCVA) was 7/10 (range 4/10–9/10) and mean intraocular pressure (IOP) was 17 mmHg, with one eye demonstrating increased IOP of 32 mmHg. Clinical findings included bilateral diffuse mid-peripheral iris transillumination, conjunctival hyperemia, unresponsive pupils, and pigment dispersion into the anterior chamber. Two cases presented blue-colored irides. Gonioscopy showed pigment deposition at the trabecular meshwork. Anterior segment optical coherence tomography (OCT) revealed a normal iris configuration in all cases.
In Greece, BAIT has been infrequently described, with the highest prevalence being reported in Türkiye. The etiopathogenesis remains unknown, but the typical geographical distribution raises suspicion of a genetic predisposition. BAIT could be considered a drug-related adverse event or an ocular manifestation of viral infections, such as COVID-19. Clinical findings may vary, though differential diagnosis can be quite challenging. In cases with elevated intraocular pressure, topical treatment is usually adequate, although surgical approaches have been reported in the literature. All of our cases fit the clinical features of BAIT. Interestingly, two of the patients had light blue iris color.
Understanding the clinical manifestations of the disease and its geographic spread facilitates a prompt clinical diagnosis, preventing unnecessary diagnostic tests. Although BCVA is typically well preserved in BAIT, persistent photophobia may lead to severe visual impairment. Further research is necessary to elucidate the exact etiopathogenesis of BAIT and explore genetic factors that may predispose individuals to this condition.
Bilateral acute iris transillumination (BAIT) is usually associated with moxifloxacin intake or respiratory tract infections, such as COVID-19, and predominantly affects middle-aged women.BAIT follows a typical geographical distribution and has been reported mostly in Türkiye, while the prevalence in Greece may be underestimated.Further studies are needed to explore genetic mutations linked to BAIT predisposition.Various ocular manifestations have been described, though differential diagnosis can often be challenging.Light-colored irides can also be affected, contrary to previous speculations.Although visual acuity is typically well preserved, patients experience significant visual impairment, primarily due to photophobia.
Bilateral acute depigmentation of the iris (BADI) and bilateral acute iris transillumination (BAIT) are conditions within the spectrum of the same entity. In the literature, the first case was reported in 2004 [1], but BADI and BAIT were initially described as new separate entities in 2005 by Tugal-Tutkun et al. [2]. In recent years, interest in the disease has risen, especially after the COVID-19 pandemic, although the etiopathogenesis remains unclear. The majority of the reported cases are associated with recent use of fluoroquinolones or respiratory tract infections, mostly caused by SARS-CoV-2. Clinical findings suggestive of the disease include ciliary injection, near complete iris transillumination, pigment dispersion in the anterior chamber, pigment accumulation in the trabecular meshwork, irregular pupil margins, and occasionally, elevated intraocular pressure. The differential diagnosis, which includes herpetic iridocyclitis, acute uveitis, and pigment dispersion syndrome, can often be challenging and requires a thorough medical history, ophthalmic examination, and laboratory workup.
The aim of this article is to report a case series of five female patients who presented with symptoms suggestive of BAIT following the intake of systemic moxifloxacin, in order to contribute to the existing literature on this rare, newly recognized condition. Unlike other similar reports, two of the patients had light blue iris color. These five cases presenting in Greece enhance the typical geographical distribution, contributing to a higher suspicion of this condition. We hypothesized that the prevalence of BAIT in the Greek population is higher than expected and this disease is underdiagnosed, due to the lack of adequate reports in the literature.
A 47-year-old female patient was referred to the Uveitis Department for further investigation. The patient presented with a 10-day history of rapid-onset severe bilateral photophobia and redness. It was initially diagnosed as acute bilateral anterior uveitis and treated with high doses of topical dexamethasone and cyclopentolate prior to her visit to the department. A detailed medical history revealed an upper respiratory tract viral infection treated with oral moxifloxacin 400 mg daily for 3 days, 2 weeks before the initiation of her ocular symptoms. No significant past medical or ophthalmic history was reported. On clinical examination, best corrected visual acuity (BCVA) was 8/10 in the right eye (OD) and 9/10 in the left eye (OS), while intraocular pressure (IOP) was 20 mmHg and 17 mmHg, respectively. Slit-lamp examination revealed mild conjunctival hyperemia, unremarkable corneas, pupils poorly responsive to mydriasis, diffuse mid-peripheral iris transillumination, and extensive posterior synechiae (270° OD, 180° OS) with fewer than five inflammatory cells, no flare, and numerous pigmented cells floating in the anterior chamber (Fig. 1a–d). Gonioscopy showed dense pigment deposition at the trabecular meshwork, especially inferiorly. The vitreous was clear, free of cells, and fundoscopy was unremarkable. Anterior segment optical coherence tomography (OCT) revealed a normal iris configuration without posterior bowing (Fig. 1e, f).Fig. 1Slit-lamp photos demonstrating mid-peripheral iris transillumination, circularly (right eye) and mainly on the nasal portion of the iris (left eye). Posterior synechiae are also observed, 270° and 180° nasally on the right and left eye, respectively (a, b). Installation of mydriatic drops showed good pupil response of the unaffected portion of the iris, bilaterally (c, d). Anterior segment OCT imaging was normal (e, f)
A 39-year-old female patient presented to the Emergency Department complaining of bilateral photophobia and ocular pain after treatment with systemic moxifloxacin for a respiratory tract infection. The last dose was received 3 days before the onset of symptoms, and the treatment duration was 7 days of oral intake. Her general medical history was unremarkable. During clinical examination, BCVA was 9/10 for both eyes and IOP was 32 mmHg and 18 mmHg for the right and left eye, respectively. Slit-lamp examination revealed severe conjunctival injection, pigment dusting on the corneal endothelium bilaterally, and pigmented cells floating in the anterior chamber (3+ OD, 1+ OS), with minimal inflammatory cells (0.5+ OD, none OS). The patient also presented pigment on the anterior lens capsules, more pronounced in her right eye (Fig. 2a, b). Gonioscopy showed excessive hyperpigmentation in the trabecular meshwork, especially in the right eye (Fig. 2c, d). Both pupils were mid-dilated and unresponsive to mydriatic instillation. Faint mid-peripheral iris transillumination defects were observed bilaterally. Examination of vitreous and fundus failed to identify any pathological findings. Anterior segment OCT did not exhibit any iris configuration abnormalities (Fig. 2e, f).Fig. 2Slit-lamp photos demonstrating fixed mid-dilated pupils bilaterally and pigment deposition on the anterior lens capsule, more profound on the right eye (a, b). Inferior angle exhibits increased pigment deposition, more profound on the right eye, making the structures of the angle indistinct (c, d). Anterior segment OCT imaging was normal (e, f)
A 75-year-old female patient was referred to the Uveitis Department due to significant visual discomfort and photophobia initiated 2 months ago. The patient had a history of bilateral acute onset of pain, redness, and photophobia that occurred after 2 weeks of treatment for pneumonia with intravenous moxifloxacin, followed by oral treatment of 400 mg daily. Symptoms appeared several days after the discharge, and most of them resolved without treatment. No additional medical or ocular history was reported. At presentation, BCVA was 5/10 and 4/10 while IOP was 14 mmHg and 16 mmHg for OD and OS, respectively. On slit-lamp examination, no findings of active inflammation were observed, but only excessive iris atrophy and diffuse iris transillumination defects bilaterally (Fig. 3a, b). The presence of lens nuclear sclerosis 2+ was noted. Instillation of mydriatic eye drops showed poor dilation bilaterally. Gonioscopy revealed increased pigment deposition in the trabecular meshwork and a Sampaolesi line bilaterally (Fig. 3c, d). Fundoscopy and further examination of the posterior segment were unremarkable. Anterior segment OCT identified iris thinning with a normal configuration (Fig. 3e, f).Fig. 3Excessive and diffuse iris transillumination is present on slit-lamp photos (a, b). Gonioscopy photos of the inferior angles, showing hyperpigmentation with a Sampaolesi line (c, d). Anterior segment OCT imaging revealed iris thinning with a normal configuration (e, f)
A 67-year-old female patient presented to the Uveitis Department as a referral from another ophthalmologist. Her predominant symptoms were chronic photophobia and blurred vision. She mentioned an episode of ocular pain and redness 1 year ago, which occurred immediately after treatment with intravenous moxifloxacin. She also had a history of dermatomyositis. During clinical investigation, BCVA was 6/10 and 5/10 for the right and left eye, respectively, and IOP was 12 mmHg bilaterally. On slit-lamp examination, no signs of active inflammation were observed, anterior chamber was free of cells, and a nuclear cataract 2+ was present on both eyes. Nevertheless, there was pigment deposition on the anterior lens capsule and diffuse iris transillumination, equally evident in both eyes, while the pupils were unresponsive to light (Fig. 4a, b). Gonioscopy exhibited hyperpigmentation bilaterally, more profound in the right eye (Fig. 4c, d). Further examination of the posterior segment did not reveal any abnormalities, and iris formation, as captured with anterior segment OCT, was normal (Fig. 4e, f).Fig. 4Slit-lamp photography showing faint, diffuse, mid-peripheral iris transillumination and mid-dilated pupils, bilaterally (a, b). Gonioscopy assessment revealed hyperpigmentation of the inferior angle bilaterally (c, d). Anterior segment OCT displaying a normal iris configuration (e, f)
A 72-year-old female patient presented to the Emergency Department complaining of ocular pain. She disclosed a history of breast and urinary bladder cancer and Hashimoto’s disease. In addition, she was hospitalized for pneumonia 10 days ago and received treatment with systemic moxifloxacin orally throughout her hospital stay. Proceeding to a full ophthalmological examination, BCVA was 6/10 and 8/10 for the right and left eye, respectively, and IOP was 14 mmHg for both eyes. Slit-lamp examination revealed conjunctival injection, corneal pigment dusting, and pigmented cells 1+ in the anterior chamber (Fig. 5a, b). Severe diffuse iris transillumination was obvious and pupillary light reaction was decreased (Fig. 5a, b). Gonioscopy showed moderately pigmented trabecular meshwork (Fig, 5c, d). Pigmentation was also found in the anterior lens capsule. All ocular manifestations mentioned above appeared bilaterally. Fundoscopy revealed the presence of epiretinal membrane in the right macula. Imaging with anterior chamber OCT was normal (Fig. 5e, f).Fig. 5Anterior segment photos demonstrate mid-peripheral and diffuse iris transillumination, poor mydriasis after mydriatic drop instillation, and pigment cells floating in the anterior chamber (a, b). Hyperpigmentation of the inferior angle is observed on gonioscopy (c, d). Anterior segment OCT imaging was normal (e, f)
A complete uveitis workup was performed for each patient, and treatment with mild topical corticosteroid drops was initiated for ocular symptoms, where necessary. Additionally, case 2 was treated with a combination of latanoprost, brinzolamide, brimonidine, and betaxolol for 6 months. All patients were monitored for a minimum of 1 year.
The study was approved by the institutional review board and conducted in accordance with the Helsinki Declaration. All participants gave informed consent for participation and publication.
BAIT and BADI have primarily been described in Türkiye [3] and Europe, although there are known cases in India [4], Brazil [5], and the USA [6]. In Greece, there are a few cases reported. More specifically, according to the existing literature, only 17 Greek patients have presented with symptoms indicating these conditions [7, 8]. Therefore, this paper contributes with five more cases native in Greece. As long as etiology remains unclear, composition of epidemiological maps could be essential.
Recently, after the COVID-19 era, BAIT has come to the forefront, with increasing case reports suggesting this diagnosis [8–12]. Before the pandemic, the entity was poorly described, and for this reason, it is possible that it escaped identification by not being included in the differential diagnosis. The escalating prevalence could be related to the wide use of fluoroquinolones, commonly prescribed for treating complications of respiratory tract infection caused by SARS-CoV-2 virus. Another explanation could be that COVID-19 infection itself constitutes the causative factor of the depigmentation, and BAIT could be an ocular manifestation of this multisystem disease. However, the exact mechanism for this hypothesis remains unclear.
The etiopathogenesis of BAIT and BADI has not yet been defined. According to the literature, the initiation of symptoms usually follows a respiratory infection or fluoroquinolone intake [3]. In rare cases, the incidents were described as spontaneous [13–15] or have been attributed to exposure to insecticide spray [16] and pitcher plant extract injections [17]. The role of fluoroquinolones as causative factor is further supported by the reference of unilateral BAIT-like cases after intracameral moxifloxacin injection [18–20]. It could reasonably be assumed that the entity has a genetic predisposition, since it has a strong sex preference and it adopts a quite defined geographical distribution. This suggestion is reinforced by a simultaneous onset of BADI in two siblings, reported in 2018 [21]. All cases described herein are associated with moxifloxacin administration after respiratory tract infection. However, none of them tested positive for COVID-19 infection. They are all Caucasian females, residents of southern Greece, following the already described geographic pattern [3], and probably share some common genes.
It is crucial that further studies be conducted in order to investigate the exact mechanism and possibly to identify specific mutations that lead to BAIT predisposition. A potential starting point could be genetic mutations that are known to cause iris diseases and pigment dispersion. If this hypothesis is confirmed, a specific part of the population could avoid fluoroquinolone use in favor of alternative antibiotic treatments. A multicenter genetic analysis of Turkish and Greek populations would be of great interest in the elucidation of the predisposition pattern.
It seems challenging to distinguish between BAIT and BADI cases, as both conditions present with similar symptoms, such as photophobia, bilateral conjunctival hyperemia, and circulating pigment in the anterior chamber. In BADI, the iris stroma shows a diffuse or patchy depigmentation with clearly distinguishable margins, typically observed from the iris root to the collarette, sparing the peripupillary iris. There are no posterior synechiae or iris transillumination, as only the iris stroma is affected. Later, iris changes may be subtle or unnoticed, as re-pigmentation has been observed. Pupils are round or slightly irregular, with normal reactions. In contrast, BAIT is characterized by diffuse iris transillumination, indicating iris epithelial pigment loss, and irregularly mydriatic pupils that are poorly responsive or unresponsive to light, due to iris sphincter muscle atrophy. These features are not reversible and are in associated with persistent photophobia. Posterior synechiae may also develop. Elevated IOP can be present in both conditions, but tends to be higher and potentially become uncontrollable in BAIT. Compared to BADI, patients with BAIT exhibit more severe symptoms and signs [3, 22].
Regarding our patients, all of them experienced similar symptoms that led them to seek medical advice. They mainly reported bilateral ocular pain and photophobia, combined with redness and blurred vision, although BCVA was not affected. In cases 3 and 4, the relatively decreased visual acuity was related to the presence of nuclear cataract, matching the patients’ age. After clinical evaluation, bilateral diffuse iris transillumination was observed, more severe in cases 3 and 5 and less severe in case 2. Additionally, pupil light reaction was abolished in cases 2 and 4 and poor in cases 3 and 5. These signs are indicators of iris epithelial involvement and atrophy of the iris sphincter muscle. The only case that developed posterior synechiae was case 1. We believe that all patients reported herein fit the clinical features of BAIT.
Concerning IOP, it was elevated only in the right eye of case 2, where the amount of pigment in the trabecular meshwork was excessive. The patient had no previous history of elevated IOP, and this episode was sufficiently controlled with the use of multiple anti-glaucoma eye drops. Drug independence was achieved 6 months later. Eventually no glaucomatous optic disc neuropathy, visual field, or OCT retinal nerve fiber layer (RNFL) defects were developed. According to the existing literature, most cases of intraocular hypertension in BAIT are adequately treated with topical medication and fewer with oral anti-glaucoma agents [23]. Occasionally, trabeculectomy with anti-metabolite is required, with safe and effective results long-term [24]. Furthermore, other anti-glaucoma interventions have been proposed, such us selective laser trabeculoplasty [25], gonioscopy-assisted transluminal trabeculotomy [26], and trabeculotomy ab interno with the Trabectome [27]. However, as all these approaches were anecdotal, they need to be further tested.
In order to reach BAIT diagnosis, other causes of painful red eyes and iris depigmentation should be ruled out. These diseases include episcleritis/scleritis, acute iridocyclitis, uveitis of viral origin (varicella-zoster virus [VZV], herpes simplex virus [HSV], or cytomegalovirus [CMV]), Fuch’s uveitis syndrome, angle-closure glaucoma, and pigment dispersion syndrome (PDS). Absence of inflammatory signs, such as keratic precipitates, bilaterality, heavy pigment deposition, lack of herpetic infection history, and rapid onset of diffuse iris depigmentation, are diagnostic clues to differentiate BAIT from viral uveitis. Features that rule out PDS are injection, severe photophobia, and absence of posterior iris bowing or typical patterns such as Scheie stripe, Zentmayer ring, or Krukenberg spindle. Additionally, PDS is presented with radial mid-peripheral iris transillumination, typically in young myopic males, while BAIT mostly affects female patients around 40 years of age [28]. The main differential diagnostic characteristics are summarized in Table 1. In any case, a history of respiratory illness and/or fluoroquinolone use should raise suspicion of BADI or BAIT.Table 1Comparison of the typical features in BAIT, PDS, and viral uveitisBAITPDSViral uveitisAge/sexMiddle-aged/femaleYoung/maleMiddle-agedMedical historyRespiratory infection and/or fluoroquinolone intakeExercise-induced episodesHerpetic infectionAcute onsetYesNoYesBilateralityYesYesNoConjunctival injectionYesNoYesInflammatory signsNoNoYesPhotophobiaYesNoYesIris transilluminationDiffuseSpoke-likeLocalized patchyPosterior iris bowingNoYesNoGonioscopyDense pigment depositionDense pigment deposition, Sampaolesi lineNo typical findingsBAIT bilateral acute iris transillumination, PDS pigment dispersion syndrome
All of our cases were female patients, reported systemic moxifloxacin intake (two cases intravenously and three orally), and presented normal iris anatomy on anterior segment OCT along with characteristic diffuse iris transillumination. There were minimal signs of inflammation only in cases 1 and 2 with 0.5+ cells in the anterior chamber. The posterior segment appeared unremarkable in all of them, with the exception of an epiretinal membrane in the right macula in case 5. Three out of five cases were initially misdiagnosed as acute uveitis, indicating that detailed history-taking and ophthalmological examination and imaging are crucial in order to reach the diagnosis of BAIT. Indeed, the laboratory workup for uveitis came back negative in all of our patients. All five patients are monitored on a regular basis in the Uveitis Department, and none of them presented new symptoms. Iris atrophy remained stable, keeping up with the typical clinical course of BAIT.
Patients in almost all of the cases reported in the literature originally had brown eyes, and the depigmented areas caused a grayish discoloration. Interestingly, patients in case 3 and case 5 initially had light blue eyes. Although BCVA is well preserved, persistent photophobia, due to iris transillumination and fixed mydriatic pupils, remained in all cases and has had a negative impact on the daily activities of the patients. Standard clinical assessments may underestimate the severity of light sensitivity, which can lead to significant visual impairment and reduce the quality of life.
One of the limitations of this study is that polymerase chain reaction (PCR) testing for herpesviruses in aqueous humor samples was not performed due to the unwillingness of the patients. Although PCR testing was essential in order to exclude herpetic or other viral causes of anterior uveitis, our definitive diagnosis was mostly clinical, based on patients’ history and clinical findings. Additionally, every patient was monitored for a period of 1 year with no recurrence of their ocular symptoms or any change in their condition.
BAIT is characterized by iris pigment epithelial depigmentation causing diffuse iris transillumination. Middle-aged female patients are predominantly affected, while moxifloxacin intake and viral infections seem to trigger the disease. It usually follows a well-defined geographical pattern, including Greece. Residents of these areas presenting with typical BAIT symptomatology are highly likely candidates for clinical diagnosis and could potentially avoid unnecessary therapy and workup. BAIT can also affect light-colored irides, in contrast with prior speculations. Any form of fluoroquinolone should be used sparingly, taking into consideration the severe visual discomfort that can remain after an episode of BAIT. Further research should be conducted for the exact etiopathogenesis to be found and the genetic correlation to be identified. Thus, susceptible individuals for BAIT should avoid the use of incriminating substances.