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a–h Optical coherence tomography (OCT) scans of the macula densa of both eyes in time course. a, b OCT scans at diagnosis. Large cystic spaces are seen in the outer reticular layer and small cystic spaces in the inner nuclear layer. Retinal thickness is lower outside the perifoveal area. c, d OCT scans at 1 week following diagnosis, when paclitaxel was ceased. e, f One week after cessation of paclitaxel. g, h Three weeks after cessation of paclitaxel. Cystic spaces and retinal thickness gradually decreased.
Source publication
We present a case of a metastatic breast cancer patient with cystoid macular edema (CME) occurring during treatment with paclitaxel and bevacizumab. She had a history of neoadjuvant chemotherapy and partial mastectomy plus axillary lymph node dissection for stage IIB left-breast cancer. Twenty-four months later, she was diagnosed with multiple bone...
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Citations
... For some authors, a 3-month therapy is sufficient to induce T-CME [8], and others [11][12], suggest that a cumulative dose seems responsible for the toxic effects of this therapy. "Indeed, when a cumulative dose of Docetaxel reached 200 mg/m2, a significant decrease in the colloid osmotic pressure values of plasma (Plasma COP) and interstitial fluid (Interstitial COP), hemoglobin, hematocrit, albumin and total proteins decrease significantly" [13]. These authors suggested that an increase in plasma volume was followed by an accentuation of fluid filtration towards the interstitial medium [12]. ...
... SD-OCT images show larger hyporeflective cysts located in the outer nuclear layer and smaller cysts in the inner nuclear layer, with an intact outer retinal layer. The involvement is focal and symmetrical, centered around the fovea [8][9][10][11][12][13][14][15]. These same SD-OCT results were found in our patient. ...
... Acetazolamide, prednisolone, triamcinolone, dorzolamide and intravitreal injection of anti-Vascular endothelial growth factor (anti-VGEF) [10][11][12][13][14][15], have been used in the treatment of these T-CME, however, none of these products has proven effective. In most reported cases, resorption of macular edema occurs spontaneously after discontinuation of taxanes without any ocular treatment within 1.5 weeks to 6 months) [10][11][12][13][14][15]. ...
Docetaxel and paclitaxel are taxanes. They are widely used chemotherapeutic agents that have been shown to be effective for various types of solid malignancies. Docetaxel-related bilateral toxic cystoid macular edema (T-CME) has been reported as a rare and unusual adverse reaction. We report a case of 43-year women treated for breast cancer with docetaxel and developed T-CME. She was treated with two cycles of Docetaxel 150 mg, Pertuzumab 420 mg and Trastuzumab 360mg. Three days after 2nd cycle she complained of diminution of vision. Her both eye visual acuity was 20/200. Fundus examination showed macular edema which was confirmed with SD-OCT and fluorescein angiography. After fourth cycle Docetaxel was stopped by treating physician. CME was completely resolved by three months. Several studies suggest that a cumulative dose seems necessary for the onset of the toxic effect of this drug. To our knowledge, we report the first case of Docetaxel-induced T-CME occurring within less than 1 month, with a very low cumulative dose. This suggests that no cumulative dose is needed for macular edema to appear.
... CMO appears petaloid on fundus fluorescein angiography (FFA) due to the vertical structure of the Müller cells that become stretched as a result. However, CMO on OCT without FFA leakage is also reported in adults who undergo taxane chemotherapy [31] and Vitamin B3 (Niacin) in the treatment of high cholesterol [32]. The underlying hypothesis is that these agents are toxic to Müller cells without disrupting the blood retinal barrier (BRB) [33]. ...
Objective
To investigate the relationship between cystoid macular oedema (CMO) measured in preterm infants using hand-held spectral domain optical coherence tomography (HH SD-OCT), with gestational age at birth (GA), birthweight (BW), diagnosis of retinopathy of prematurity (ROP) and the presence or absence of the external limiting membrane (ELM).
Methods
We conducted a prospective mixed cross-sectional/longitudinal observational study of 112 participants (23 to 36 weeks GA; n = 25 with, and n = 87 without, CMO). Retinal images were acquired using 344 HH SD-OCT ( n = 66 with and n = 278 without, CMO) between 31 to 44 weeks postmenstrual age (PMA). CMO type (‘fovea’ and ‘dome’) was measured using thickness, width, area and peak.
Results
CMO was observed in 22.9% of preterm infants, and 19.2% of images. The mean values for thickness, width, area and peak of ‘dome’ CMO were 128.47 µm (SD +/- 34.23), 3624.45 µm (SD +/- 1323.03), 0.49 mm ² (SD +/- 0.28) and 279.81 µm (SD +/- 13.57) respectively. The mean values for thickness, width, area and peak of ‘fovea’ CMO were 64.37 µm (SD +/- 17.11), 2226.28 µm (SD +/- 1123.82), 0.16 mm ² (SD +/- 0.11) and 95.03 µm (SD +/- 26.99) respectively. Thickness, area width and peak were significantly greater for ‘dome CMO compared with ‘fovea’ CMO ( P < 0.0001 for thickness, area and peak; P < 0.01 for width). Area and width significantly decreased with PMA for ‘dome’ and ‘fovea’ CMO ( p = 0.0028; p < 0.001 respectively). No association was found between the presence of ROP and the detection of CMO or detection of CMO with absence of ELM.
Conclusions
HH -OCT in preterm infants demonstrates that the severity of CMO appearance improves each week for both fovea and dome CMO.
... İlaca bağlı KMÖ genellikle bilateraldir, fundus floresein anjiyografide genellikle sızıntı yoktur veya hafiftir, retinanın iç tabakaları yerine dış retinada kistik boşluklar vardır. [9] İlaç kesildikten sonra ödemde spontan rezolüsyon olması da ilaca bağlı maküler ödem tanısını desteklemektedir. [10] Bu yazıda KMÖ ile ilişkili olduğu bildirilen çeşitli ilaçlara dair bilgi verilmesi, güncel literatür bilgileri ışığında patogenez ve tedaviye dair klinik verilerin tartışılması amaçlanmıştır. ...
... Taksanların kullanımına bağlı KMÖ oluşumu nadir olarak görülmektedir ve paklitaksel kullanımında daha sık görülmektedir. [9] Taksanlar ile ilişkili KMÖ, bilateral olarak görülmektedir. [32] Oluşum mekanizması henüz net olarak bilinmemektedir ancak kan-retina bariyerini veya Müller hücrelerini etkileyerek makuler ödeme yol açtığı düşünülmektedir. ...
... [33] İlaç kesilmesine rağmen gerilemeyen persistan KMÖ' de oral veya topikal karbonik anhidraz inhibitörleri, non-steroid anti-inflamatuar ilaçlar, subtenon triamsinolon enjeksiyonu ve topikal dorzolamid kullanımının etkili olduğu bildirilmektedir ancak henüz etkinliği ispatlanmış bir tedavi rejimi yoktur. [9,31,32,34] ...
Kistoid makula ödemi (KMÖ), genellikle oküler patolojilerle veya sistemik hastalıklarla ilişkili olarak gelişen bir bozukluktur. Çeşitli topikal veya sistemik ilaçların da kistoid makula ödemi oluşumuna sebep olduğu bilinmektedir. Bir anti-hiperlipidemik bir ilaç olan niasin (nikotinik asit), antineoplastik olarak kullanılan taksanlar (paklitaksel/dosetaksel), oral antidiyabetik ilaçlardan glitazonlar, demir ve alüminyum şelatörü deferoksamin ve multipl skleroz tedavisinde kullanılan fingolimod, sistemik olarak kul-lanılan ve makula ödemi ile ilişkili olduğu gösterilen ilaçlardır. Ayrıca epinefrin ve prostaglandin analogları KMÖ ile ilişkili olduğu bilinen oküler ajanlardır. Bu makalenin amacı, ilaçlar ile ilişkili kistoid makula ödemi gelişimi hakkında mevcut bilimsel kanıtlara dair genel bir bakış açısı sağlamak ve olası patofizyolojik mekanizmalar ve terapötik yaklaşımlara dair genel bilgi sunmaktır. Anahtar Kelimeler: advers etki, ilaç, makuler ödem, retina
Cystoid macular edema (CME) is a disorder that usually develops in association with ocular pathologies or systemic diseases. Various topical or systemic drugs are also known to lead to the formation of cystoid macular edema. Anti-hyperlipidemic drug niacin (nicotinic acid), antineoplastic agents taxanes (paclitaxel/docetaxel), oral antidiabetic drugs glitazones, iron, and aluminum chelator deferoxamine, and fingolimod used in the treatment of multiple sclerosis are drugs used systemically and shown to be associated with macular edema. In addition, epinephrine and prostaglandin analogs are ocular agents known to be associated with CME. The purpose of this article is to provide an overview of the available scientific evidence on the development of drug-induced cystoid macular edema and to provide insight into possible pathophysiological mechanisms and therapeutic approaches.
... Taxanes have not been previously reported as inducers of uveitis. Paclitaxel-based chemotherapy is known to cause ocular side effects including meibomian gland dysfunction [4], canalicular obstruction [4], diplopia [4], keratitis [9], CME [10], scintillating scotoma [11], and possibly glaucoma [12,13]. Das et al. recently reported bilateral severe ischaemic retinopathy and optic neuropathy in a 72-yearold patient treated with combination cyclophosphamide and paclitaxel therapy for breast carcinoma [14]. ...
... CME appears to be the most common retinal complication of both paclitaxel and docetaxel, despite occurring at a very low rate amongst treated patients [15]. It is often bilateral, and can be angiographically silent [10,[16][17][18]. The CME occurs several months after starting paclitaxel treatment, consistent with the timeline of uveitis onset in our patient. ...
Background
To report a case of bilateral intermediate uveitis without cystoid macular edema secondary to paclitaxel therapy, and its successful management with oral corticosteroids.
Case presentation
A 66-year-old female developed bilateral intermediate uveitis with reduced best corrected visual acuity to 20/40 right and 20/200 left, following 12 cycles of paclitaxel therapy for breast carcinoma. Optical coherence tomography demonstrated no cystoid macular edema in either eye, and fundus fluorescein angiography showed localized retinal vascular leakage. Resolution of uveitis and improvement of visual acuity followed treatment with oral prednisolone for two months. Fourteen months after presentation, right and left visual acuities had returned to 20/32 and 20/40, respectively, and there was no recurrence of the uveitis.
Conclusions
This is the first reported case of bilateral intermediate uveitis in a patient treated with paclitaxel. Drug-induced uveitis should be considered in patients with visual symptoms in the setting of taxane chemotherapy, and oral corticosteroids are a safe and effective treatment.
... Dose reduction or discontinuation of incriminated drugs may help reduce the severity and the dura-tion of side effects. Generally, the ocular side effects caused by taxane chemotherapy can be relieved after stopping the administration of chemotherapy [18]. All those side effects mentioned above may not threaten the life span of the patients while may cause various troubles in their life after anti-cancer treatment. ...
In recent years, in-depth research on anti-tumor therapy has brought the emergence of new active chemotherapeutic agents and combination regimens. However, as one of them, taxane drugs are widely used in clinical practice, but it should be noted that many side reactions caused by their application bring some difficulties to routine management. Among the side reactions related to taxane anti-tumor therapy, ocular adverse reactions are occasionally reported and are not life-threatening but may seriously affect patients’ life quality. Thus, the continuation, reduction and cessation of taxane chemotherapy still need to be further evaluated by ophthalmologists and oncologists once the side effects show up. To prevent ocular side reactions, close attention should be paid to complications during medication. To facilitate the oncology department and ophthalmologists to comprehensively understand the ophthalmic adverse reactions of taxane drugs and their possible mechanisms and improve drug use efficiency, we collected relevant literature and reviewed and provided some suggestions for the monitoring and managing of ophthalmic toxicity.
... Furthermore, Müller cells play an important role in macular dehydration via metabolic pumps. 10 These conditions are induced by microvascular occlusion or underlying inflammatory disease. 11 The typical fluorescein angiographic appearance of CME consists of small focal leaks that increase in size and intensity early on, resulting in late pooling and a characteristic flower-petal pattern with or without leakage surrounding the optic nerve. 1 While for drug-induced CME, several papers have reported that CME was not observed to be associated with leakage on fluorescein angiography. ...
Purpose
To report the first known case of bilateral cystoid macular edema in a patient undergoing long-term loratadine treatment.
Observations
A 49-year-old Chinese woman who had been undergoing treatment with loratadine for the past 6 years presented with decreased visual acuity and bilateral cystoid macular edema (CME). Upon cessation of loratadine, macular edema partially resolved, and visual acuity markedly improved. Fundus autofluorescence (FAF), optical coherence tomography (OCT), and fluorescence fundus angiography (FFA) were used to document the severity of CME and its subsequent resolution after cessation of loratadine therapy.
Conclusions
and Importance: Long-term use of loratadine might cause CME that partially resolves with discontinuation of the drug. The pathophysiology of drug-induced CME without leakage remains unclear. Dysfunction of histamine receptor1-expressed retinal neurons and the associated signal transduction, toxicity to Müller cells or RPE cells with subsequent intracellular fluid accumulation, and subclinical damage to the blood-retina barrier leading to leakage of extracellular fluid, have been proposed.
... Cystoid macular edema (CME) is also a known complication of DTX chemotherapy [30], and it can be diagnosed via fluorescein angiography or optical coherence tomography, where fluid accumulation in multiple cyst-like spaces is observed in the macula [18]. Several clinical cases have reported taxane-induced CME [10,20,21,31,33,9]. In one of these cases, a patient without retinopathy who had received hydroxychloroquine for rheumatoid arthritis for 33 years developed bilateral vision loss after receiving DTX chemotherapy for breast cancer. ...
Docetaxel (DTX) is a highly effective anti-tumor drug frequently used in clinical practice. Previous reports indicated that complications after DTX therapy could be related to retinal pigment epithelial (RPE) cell dysfunction, although no direct reports of this relationship have been published. In this study, human embryonic stem cell–derived RPE (hESC-RPE) cells were used to explore the effects of DTX on their morphology, viability, apoptosis, proliferation, and cell cycle. We also searched for DTX residue in these cells. DTX had a time- and concentration-dependent inhibitory effect on hESC-RPE cell viability, and the cells only survived after 24 h of stimulation with 0.1 mg/mL of DTX. Following drug withdrawal, the cell morphology continued to change, and hESC-RPE cell damage was observed. High-performance liquid chromatography/mass spectrometry showed that some unmetabolized DTX remained in hESC-RPE cells after the 48 and 120 h DTX treatments. Flow cytometry and immunofluorescence revealed that DTX significantly enhanced apoptosis, and the Cell Counting Kit-8 assay and flow cytometry indicated that DTX inhibited cell proliferation and blocked the cell cycle. These results suggest that DTX has a direct cytotoxic effect on hESC-RPE cells. Thus, RPE cell damage after DTX treatment may present an important safety problem that could potentially limit the application of this drug in clinical practice. The findings of this study suggest that clinicians should weigh the benefits of DTX versus the risks of ocular adverse reactions rationally. Timely diagnostic evaluation and drug withdrawal will be conducive to the recovery of patients' visual acuity.
... It is worth noting that there are also reports of no vision recovery even after macular edema has subsided after paclitaxel discontinuation (37). Moreover, in some cases of delayed CME diagnosis, macular degeneration progresses, and vision loss is irreversible (38). ...
Angiographically silent cystoid macular edema (CME) is a rare complication from nab-paclitaxel. Here we report a 45-year-old woman with breast cancer who developed CME after several months of treatment with albumin-bound paclitaxel (nab-paclitaxel). Her visual acuity did not improve significantly with the cessation of nab-paclitaxel and intravitreal ranibizumab treatment. Then, brinzolamide eye drops were prescribed. One month later, her vision improved, with the macular edema significantly subsided. Finally, we reviewed other cases of CME induced by nab-paclitaxel that have been reported in the literature and discussed the underlying pathogenesis of nab-paclitaxel-induced CME.
... While the causes of taxane-related CME are unclear, subtle capillary leakage and effect of taxane toxicity on Müller cells or the retinal pigment epithelium (RPE) have been suspected to play a role [5][6][7][8][9][10][11][12]. Although several treatment options have been reported for taxane-related CME, including oral carbonic anhydrase inhibitors (CAIs) [10], nonsteroidal antiinflammatory drugs [13], sub-Tenon's injection of triamcinolone acetonide [14], intravitreal bevacizumab [15], and pentoxifylline [9], their effectiveness in resolution of CME remains to be proven [6][7][8][9]. Dorzolamide, a topical CAI available as eye drops, is used to lower the intraocular pressure in glaucoma and ocular hypertension; some reports suggest that topical dorzolamide is also effective against taxane-related CME [11,12,15]. ...
Background
Cystoid macular edema is a rare, vision-threatening side effect of the taxane family of anticancer agents. There is no established treatment or standard treatment protocol for taxane-related cystoid macular edema. Here, we report two cases of taxane-related cystoid macular edema that were treated with topical dorzolamide.
Case presentation
In case 1, a 72-year-old Japanese woman with bilateral geographic choroiditis reported for a follow-up visit with a complaint of blurred vision in both eyes for 2 months after starting nanoparticle albumin-bound paclitaxel chemotherapy for multiple metastases of her breast cancer. Her best-corrected visual acuity had dropped from 1.2 to 0.9 in the right eye and from 1.0 to 0.4 in the left eye. Fundus examination showed no newly active geographic choroiditis lesion, but optical coherence tomography exhibited cystoid macular edema. We suspected taxane-related cystoid macular edema and terminated nanoparticle albumin-bound paclitaxel, and started topical dorzolamide treatment. Cystoid macular edema nearly resolved within 6 weeks in the right eye and within 10 weeks in the left eye after starting topical dorzolamide treatment. The resolution of cystoid macular edema without leaving a chorioretinal scar after discontinuation of paclitaxel confirmed our initial diagnosis of taxane-related cystoid macular edema. A few inconspicuous cystoid spaces persisted at the parafovea for a year after dorzolamide treatment ended, but regressed after restarting dorzolamide treatment without any side effects. Best-corrected visual acuity improved to 1.2 in the right eye and 1.0 in the left eye. In case 2, a 70-year-old Japanese man, who received nanoparticle albumin-bound paclitaxel for pancreatic cancer with multiple metastases, developed bilateral cystoid macular edema. Best-corrected visual acuity was 0.3 bilaterally. Cystoid macular edema resolved within 5 weeks after stopping nanoparticle albumin-bound paclitaxel and starting topical dorzolamide treatment confirming the diagnosis of taxane-related cystoid macular edema. Nine weeks later, best-corrected visual acuity improved to 0.8 in the right eye and 1.0 in the left eye.
Conclusions
Cystoid macular edema in each case resolved within a few months without any side effects using topical dorzolamide and terminating taxane-based chemotherapy. Topical dorzolamide appears to be a safe and effective treatment option for patients with taxane-related cystoid macular edema whose quality of life is threatened by visual disturbances.
... 3 Although most cases resolve spontaneously, several authors have used systemic or topical carbonic anhydrase inhibitors, topical anti-inflammatory agents, or intravitreal bevacizumab to accelerate resolution or when taxane therapy cannot be discontinued. 3,5 Our patient presented with CME in the right eye associated with bilateral hyperreflective changes on SDOCT that didn't respond to cessation of therapy. Even though the presence of CME can be related to the history of previous macular surgery due to its subtle presentation and it's absence in the fellow eye, its association with bilateral hyperreflective deposits raises the question if the use of both medications in a patient with prior history of macular surgery increases the risk of retinal toxicity in patients undergoing chemotherapy. ...
Purpose
To report the findings of unilateral cystoid macular edema (CME) associated with bilateral sub-foveal hyperreflectivity in a patient previously diagnosed with breast cancer and treated with docetaxel and cyclophosphamide.
Observations
A 69-year-old female on docetaxel and cyclophosphamide chemotherapy treatment for breast cancer developed blurry vision 20 days after initiation of therapy. Ophthalmic examination revealed reduced visual acuity with bilateral retinal pigment epithelium mottling and annular sub-foveal thickening in the left eye. Optical coherence tomography (OCT) showed cystoid macular changes in the right eye and central sub-macular hyperreflectivity of outer layers in both eyes. Six-months after discontinuation of therapy, OCT findings remained unchanged and visual acuity did not improve.
Conclusionsand importance
CME may occur in patients taking taxanes, but this finding associated with sub-macular hyperreflectivity of the outer layers in diagnostic testing has never been reported before. Sub-macular deposits found in this patient may be responsible for decreased vision and did not respond to cessation of therapy.
