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Fluorescein angiography (FA) images in the patient before (a) and after (b) oral acetazolamide therapy obtained at 2 min after fluorescein injection. Dye leakage in both the macular and mid-peripheral areas is decreased by the treatment, as demonstrated by remarkably decreased leakage in the macula and more definite demarcation of hyperfluorescent lesion in the mid-peripheral retina
Source publication
Background
Hydroxychloroquine (HCQ) retinopathy can accompany other retinal complications such as cystoid macular edema (CME), which leads to central visual loss. We report a case of CME with HCQ retinopathy that improved with the use of oral acetazolamide, and discussed the possible mechanisms of CME in HCQ retinopathy using multimodal imaging mod...
Citations
... Since ACZ has been widely used in clinical applications and eye diseases for many years, there is no doubt about its safety. Also, there are case reports and case series about the use of ACZ in DRP [59,60]. ...
Diabetic Retinopathy (DRP) is a disease consisting of all the structural and functional changes that develop in the retinal layer of the eye due to diabetes. DRP is the most important cause of blindness between the ages of 20-74 in the world, and the most successful standard treatment option in the treatment of DRP is intravitreal injections. To synthesize acetazolamide loaded nanoparticles to be applied intravitreal treatment of DRP and to examine the in vitro efficacy of the nanoparticles. ACZ loaded PHBV nanoparticles (PHBV-ACZ NPs) formulations were prepared. Nanoparticles with a particle size of 253.20±0.55nm. A DRP model was established and characterized in HRMEC cells. The effect of the nanoparticles on permeability has been investigated and carrier proteins in BRB due to the development of DRP has been investigated. To establish the in vitro DRP model, HRMEC was stimulated with Recombinant human 165 Vascular Endothelial Growth Factor (VEGF), thereby temporarily reducing the expression levels of endothelial junction proteins, increasing the number of intercellular spaces in the monolayers of HRMECs. It was determined that after the cells were exposed to Carbonic anhydrase inhibitors (CAI) loaded nanoparticles, permeability decreased and protein expression increased.
... However, a recent report demonstrated inner retinal thinning in patients with advanced retinopathy (Kim et al., 2023). Further, there have been multiple cases with cystoid macular edema reported from patients with hydroxychloroquine retinopathy (Parikh et al., 2016;Hong et al., 2017;Kim et al., 2018). These cases were advanced retinopathy with RPE involvement in common; accordingly, a damaged retinal pigment epithelium and breakdown of the outer retinal barrier may have allowed accumulation of fluid within the retina, also involving the inner retina. ...
Long-term use of hydroxychloroquine can cause retinopathy, which may result in severe and progressive visual loss. In the past decade, hydroxychloroquine use has markedly increased and modern retinal imaging techniques have enabled the detection of early, pre-symptomatic disease. As a consequence, the prevalence of retinal toxicity in long-term hydroxychloroquine users is known to be higher than was previously estimated. The pathophysiology of the retinopathy is incompletely characterised, although significant advances have been made in understanding the disease from clinical imaging studies. Hydroxychloroquine retinopathy elicits sufficient public health concern to justify the implementation of retinopathy screening programs for patients at risk. Here, we describe the historical background of hydroxychloroquine retinopathy and summarize its current understanding. We review the utility and limitations of each of the mainstream diagnostic tests used to detect hydroxychloroquine retinopathy. The key considerations towards a consensus on the definition of hydroxychloroquine retinopathy are outlined in the context of what is known of the natural history of the disease. We compare the current screening recommendations for hydroxychloroquine retinopathy, identifying where additional evidence is required, and the management of proven cases of toxicity. Finally, we highlight the areas for further investigation, which may further reduce the risk of visual loss in hydroxychloroquine users.
... It is interesting to note that CME in HCQ retinopathy can be in both leaking [8,9] and non-leaking form of FA [7], and our patient demonstrated the latter form. Non-leaking form of CME is uncommon, and of few causes including juvenile retinoschisis, retinitis pigmentosa, Goldman-Favre disease, and several drug toxicities such as niacin and taxane [10]. ...
... Nonetheless, treatment of CME in HCQ retinopathy has not been formally established. Topical non-steroidal anti-Inflammatory drugs (NSAIDs), intravitreal triamcinolone showed poor response [7], whereas topical or systemic carbonic anhydrase inhibitors demonstrated varying success [7][8][9]. ...
Introduction: Hydroxychloroquine (HCQ) is used for treating systemic lupus erythematosus (SLE). It can cause irreversible toxic retinopathy, we discuss the outcome of HCQ retinopathy and emphasize the distinct toxicity pattern in Asian patients. Case Series: We report a retrospective case series of two systemic lupus erythematosus (SLE) patients who presented with HCQ toxicity. Both Asian SLE patients were treated with HCQ over five years with cumulative dose of >1000 g. Both had characteristic findings on spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF). First patient had non-leaking cystoid macula edema (CME) associated with HCQ retinopathy and second patient had bull’s eye maculopathy (BEM). They exhibited different outcome after drug cessation. There was no disease progression in former whereas latter lost her central vision over two years. Conclusion: Non-leaking CME is rare and can be a sequence of HCQ retinopathy. Bull’s eye maculopathy is another manifestation of severe HCQ toxicity. Toxic damage to retina is irreversible, and may progress even after the drug is stopped, so is crucial to discontinue once toxicity is detected. Patients on HCQ warrant annual screening with multimodal imaging. There are racial differences in HCQ toxicity, hence distinct screening tests should be performed in Asian population.
... Acetazolamide is an approved drug that is used to treat retinal complications, epilepsy and other diseases, particularly in children. To date, no interference with other therapies has been reported [90][91][92]. ...
Advances in research have boosted therapy development for congenital disorders of glycosylation (CDG), a group of rare genetic disorders affecting protein and lipid glycosylation and glycosylphosphatidylinositol anchor biosynthesis. The (re)use of known drugs for novel medical purposes, known as drug repositioning, is growing for both common and rare disorders. The latest innovation concerns the rational search for repositioned molecules which also benefits from artificial intelligence (AI). Compared to traditional methods, drug repositioning accelerates the overall drug discovery process while saving costs. This is particularly valuable for rare diseases. AI tools have proven their worth in diagnosis, in disease classification and characterization, and ultimately in therapy discovery in rare diseases. The availability of biomarkers and reliable disease models is critical for research and development of new drugs, especially for rare and heterogeneous diseases such as CDG. This work reviews the literature related to repositioned drugs for CDG, discovered by serendipity or through a systemic approach. Recent advances in biomarkers and disease models are also outlined as well as stakeholders’ views on AI for therapy discovery in CDG.
... В исследовании Suzuki и соавт. было показано, что местное применение дорзоламида после витреоретинальной операции по поводу эпиретинального фиброза позволяло существенно снизить проявления макулярного отека в течение первого месяца после операции [32]. Авторы объяснили это противовоспалительным действием препарата, а именно его способностью подавлять выработку провоспалительного цитокина интерлейкина 6 [33], а кроме того, ингибированием КА IV в ретинальном пигментном эпителии (РПЭ). ...
Topical and systemic carbonic anhydrase inhibitors (CAIs) are widely used in the treatment of glaucoma for reducing intraocular pressure. This part of the review describes the characteristics of systemic CAIs, their side effects and the ways to overcome them, as well as contraindications. The use of CAIs during pregnancy is considered. Particular attention is paid to the antioxidant activity of CAIs and the promising development of hybrid forms based on the existing CAIs as a part of a multipurpose glaucoma treatment strategy.
... In fact, the rationale for using carbonic anhydrase inhibitors is to enhance RPE pumping function. 21,24,25 Whatever the exact mechanism, taxanes could potentiate the (non-leaking) CME effect of other agents (like tamoxifen 5,12 or HCQ) at the level of the RPE pump as was suggested by Buffet et al. 5 The occurrence of CME in a retinitis pigmentosa patient also supports the possibility of RPE dysfunction as a possible mechanism triggered or compounded by the taxane effect. 4 ...
Purpose:
To report a case of bilateral non-leaking cystoid macular degeneration induced by docetaxel, possibly potentiated by hydroxychloroquine.
Observations:
A 63-year-old female patient with a long-term history of rheumatoid arthritis controlled on hydroxychloroquine for 33 years with no evidence of retinopathy developed bilateral loss of vision after having been on docetaxel chemotherapy for breast cancer. Optical coherence tomography showed bilateral cystic maculopathy with no angiographic evidence of leakage on fluorescein angiography. The patient was treated conservatively with no further interventions. Marked improvement of the macular degeneration occurred over the subsequent 9 months, but without visual improvement, although a cataract likely confounded final visual acuity measurement.
Conclusions and importance:
Docetaxel-induced maculopathy has been previously reported, but with only four case reports in literature, and most often in conjunction with concurrent therapies or conditions also known to cause macular edema. This is the first case report of docetaxel-induced maculopathy in a setting of hydroxychloroquine therapy which may possibly has potentiated the effect of docetaxel to induce maculopathy. Impaired transcellular retinal pigment epithelial transport might be the cause of non-leaking cystic maculopathy.
... [1] Cystoid macular oedema (CMO) in eyes with HCQ retinopathy has been documented in several reports. [2][3][4][5][6][7] Kellner et al. reported cases with CMO secondary to HCQ retinopathy, [2] and the beneficial effect of systemic acetazolamide and topical dorzolamide in one of three patients. However, successful results with systemic or topical carbonic anhydrase inhibitor therapy for CMO associated with HCQ retinopathy have been documented in other, recent reports. ...
... However, successful results with systemic or topical carbonic anhydrase inhibitor therapy for CMO associated with HCQ retinopathy have been documented in other, recent reports. [3,4] A biodegradable intravitreal dexamethasone implant (Ozurdex; Allergan Inc., Irvine, CA) has shown effectiveness for resolution of macular oedema, including cystoid macular oedema, associated with other aetiologies. [8] Herein, we report a case of SLE complicated with CMO, for which intravitreal dexamethasone therapy was performed and resulted in complete resolution of CMO without any significant ocular complication. ...
... Several authors reported that cases with CMO showed beneficial response to systemic acetazolamide or topical dorzolamide. [2][3][4] More specifically, use of systemic and topical acetazolamide led to resolution of CME in 2 of 3 and 1 of 2 reports, respectively. The role of systemic or topical acetazolamide has been suggested to involve an enhanced pumping function of fluid mediated by the RPE, which was defective due to RPE damage in eyes with HCQ retinopathy. ...
Background
Cystoid macular oedema (CMO) is an uncommon complication associated with hydroxychloroquine (HCQ) retinopathy threatening central vision. We report a patient with HCQ retinopathy and CMO, for which an intravitreal dexamethasone implant was used, which led to complete resolution of oedema.
Case presentation
A 57-year-old woman with systemic lupus erythematosus (SLE) complaining of blurred vision in both eyes was diagnosed with bilateral HCQ retinopathy and CMO based on characteristic photoreceptor defects and cystoid spaces on optical coherence tomography, hypo-autofluorescence on fundus autofluorescence, and corresponding visual field defects. After treatment with systemic acetazolamide and topical dorzolamide, CMO showed partial resolution in the right eye. Owing to worsening renal function, an intravitreal dexamethasone implant was placed in the right eye, which resulted in resolution of CMO and visual improvement from 20/50 to 20/30.
Conclusion
Intravitreal dexamethasone implant may be effective for the treatment of CMO in HCQ retinopathy, particularly for the cases refractory to systemic or topical carbonic anhydrase inhibitors.
... Drug repositioning which is based on the use of existing and approved drugs for other diseases in therapeutic areas different from those with marketing authorization has become a possible solution [271,273,274]. Acetazolamide, a carbonic anhydrase (CA) inhibitor, can be considered a successful case of drug repositioning, since it has been used in the prophylaxis and treatment of acute mountain sickness [275], hydroxychloroquine retinopathy [276], hyperphosphatemic familial tumoral calcinosis [277] and also in the treatment of disorders associated with ataxia [278]. Now it is being evaluated for cerebellar involvement in PMM2-CDG (Clinical trial identifier 2017-000810-44). ...
Congenital disorders of glycosylation (CDG) are a group of genetic disorders that affect protein and lipid glycosylation and glycosylphosphatidylinositol synthesis. More than 100 different disorders have been reported and the number is rapidly increasing. Since glycosylation is an essential post-translational process, patients present a large range of symptoms and variable phenotypes, from very mild to extremely severe. Only for few CDG, potentially curative therapies are being used, including dietary supplementation (e.g., galactose for PGM1-CDG, fucose for SLC35C1-CDG, Mn2+ for TMEM165-CDG or mannose for MPI-CDG) and organ transplantation (e.g., liver for MPI-CDG and heart for DOLK-CDG). However, for the majority of patients, only symptomatic and preventive treatments are in use. This constitutes a burden for patients, care-givers and ultimately the healthcare system. Innovative diagnostic approaches, in vitro and in vivo models and novel biomarkers have been developed that can lead to novel therapeutic avenues aiming to ameliorate the patients’ symptoms and lives. This review summarizes the advances in therapeutic approaches for CDG.
... In the natural course of the condition, eyes with HCQ retinopathy can also develop cystoid macular edema or epiretinal membrane, which can cause further visual loss [15]. Although the retinopathy has no definitive treatment, macular edema is treatable by oral or topical carbonic anhydrase inhibitors [15,16]. Unfortunately, the long-term progression of the retinopathy has not been described, and should be further investigated so that the natural course of the disease can be better understood. ...
Maintenance of the transparency of the neurosensory retina is critical to obtaining sharp and high-resolution images. The tight endothelial barrier does not allow fluid movement into the retina. A neurovascular unit comprising Muller cell processes and the capillary endothelial cells and pericytes ensures a balanced hydrous state of the retina. It gets disturbed in metabolic, inflammatory, degenerative, and dystrophic disorders besides the retinal vascular occlusions and drug toxicities resulting in the intraretinal and subretinal fluid collection. The outer plexiform layer in the blood supply watershed zone becomes the prime site for fluid collection in the extracellular space and swelling of the cellular elements.
Macular oedema in diabetes is the most common cause of moderated visual loss. In the last 20 years, optical coherence tomography has supplanted documentation of macular oedema on stereoscopic fundus photographs and fundus fluorescein angiography. The central subfield thickness in a diameter of 1 mm on the foveal centre is the most crucial metric to diagnose and monitor the outcome of various therapeutic interventions. The standard of care intervention for macular oedema due to diabetic retinopathy and retinal vein occlusions is monthly anti-vascular endothelial growth factor injections. Intravitreal corticosteroids remain the treatment of choice for inflammatory macular oedema.
