Ophthalmic Surgery, Lasers and Imaging Retina

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Case Report 

Latanoprost-Dependent Cystoid Macular Edema Following Uncomplicated Cataract Surgery in Pseudoexfoliative Eyes

Vassilios Panteleontidis, MD; Efstathios T. Detorakis, MD, PhD; Ioannis G. Pallikaris, MD, PhD; Miltiadis K Tsilimbaris, MD, PhD

Abstract

Cystoid macular edema (CME) following uncomplicated phacoemulcification associated with latanoprost is uncommon. OCT-proven CME associated with latanoprost in 3 eyes with pseudoexfoliation after uncomplicated phacoemulcification was reported. Latanoprost was discontinued whereas topical ketorolac was administered. In all cases, CME resolved completely within the following weeks. In one case the re-administration of latanoprost lead to CME recurrence, which was treated with permanent discontinuation of latanoprost. The correlation between latanoprost and CME and the complete resolution of CME following discontinuation of the drug suggest a causative association between latanoprost and CME.

Abstract

Cystoid macular edema (CME) following uncomplicated phacoemulcification associated with latanoprost is uncommon. OCT-proven CME associated with latanoprost in 3 eyes with pseudoexfoliation after uncomplicated phacoemulcification was reported. Latanoprost was discontinued whereas topical ketorolac was administered. In all cases, CME resolved completely within the following weeks. In one case the re-administration of latanoprost lead to CME recurrence, which was treated with permanent discontinuation of latanoprost. The correlation between latanoprost and CME and the complete resolution of CME following discontinuation of the drug suggest a causative association between latanoprost and CME.

Latanoprost-Dependent Cystoid Macular Edema Following Uncomplicated Cataract Surgery in Pseudoexfoliative Eyes

From the Department of Ophthalmology, University Hospital of Heraklion, Crete, Greece.

The authors have no financial or proprietary interest in the materials presented herein.

Address correspondence to Efstathios T. Detorakis, MD, PhD, Department of Ophthalmology University Hospital of Heraklion, 71110, Heraklion, Crete, Greece.

Accepted: August 17, 2009
Posted Online: March 09, 2010

Introduction

Cystoid macular edema (CME) associated with prostaglandin-analogues (PGA) has been described following cataract surgery.1,2 Although PGA are known to disrupt blood–aqueous barrier3 there is controversy on the pathogenetic mechanism of PGA-related CME, since some studies stress the role of preservatives in the development of this condition.4 Furthermore, susceptibility of patients to the development of CME in response to PGA use varies.5 Therefore, it would be interesting to detect high-risk cases in which PGA use should be avoided. We present a series of 3 cases of latanoprost-dependent CME following uncomplicated cataract surgery in eyes with pseudoexfoliation syndrome (PEX), with a view to highlight clinical information possibly associated with increased susceptibility to CME development.

Case Series

Case 1

A 71-year-old man presented with blurred vision, left eye (OS), 3 months following ipsilateral phacoemulcification surgery. Systemic history was significant for arterial hypertension whereas no history of diabetes mellitus was reported. Ophthalmic history was significant for pseudoexfoliative glaucoma, both eyes (OU), diagnosed for the previous 4 years, under treatment with latanoprost OU. No other medications were systematically used in either eye whereas a 6-week course of combined tobramycin–dexamethazone regimen in a tapering fashion had been administered, right eye (OD), following cataract extraction. No history of uveitis or vitreoretinal disorders was reported. Preoperatively, anterior segment biomicroscopy as well as funduscopy were non-contributory for anterior segment inflammation or vitreoretinal disorders. Zonular instability was not detected preoperatively. The surgery was uncomplicated and completed without the need for maneuvers (such as iris stretching or iris hooks) to mechanically augment pharmacological mydriasis. The total operating time was 43 minute. The intraocular lens (IOL) implanted in the capsular bag was a 21.5 D AcrySof ® Natural (Alcon, Fort Worth, TX, USA).

Upon presentation, best corrected visual acuity (BCVA) was 20/20 (OD) and 20/40 (OS). Biomicroscopy was significant for intense conjunctival hyperemia with mild punctate keratopathy, as well as pseudoexfoliative material on the pupillary border (OU). Funduscopy (OS) was significant for low-grade retinal elevation at the macular area and irregular macular light reflex. Fluorescein angiography and optical coherence tomography (OCT) scan confirmed the presence of CME (Fig. 1).

Macular Optical Coherence Tomography (OCT) Scan Left Eye (OS) of Patient 1 at First Presentation (1/25/2007), Showing Cystoid Macular Edema (CME) with a Retinal Thickness of 515μm.

Figure 1. Macular Optical Coherence Tomography (OCT) Scan Left Eye (OS) of Patient 1 at First Presentation (1/25/2007), Showing Cystoid Macular Edema (CME) with a Retinal Thickness of 515μm.

Latanoprost was discontinued OS and replaced by Timolol-Dorzolamide bid. Topical ketorolac qid to the OS was also administered. Three weeks later BCVA OS had improved to 20/25 and a new OCT scan showed complete resolution of CME (Fig. 2). However, discontinuation of timolol had been advised by a cardiologist, due to induced bradycardia. The patient was therefore administered again latanoprost OU. On the next visit, 3 weeks later, he complained again of blurred vision OS. A new OCT scan confirmed the recurrence of CME (Fig. 3). Latanoprost was again discontinued OS, replaced by brimonidine tid and dorzolamide bid. Ketorolac eye drops qid were also administered to the OS. One month later, BCVA OS was 20/20 whereas a new OCT scan (Fig. 4) confirmed the complete resolution of the CME.

Macular OCT Scan of Patient 1 (OS) After Discontinuation of Latanoprost (2/15/2007), Showing CME Resolution with a Retinal Thickness of 164μm.

Figure 2. Macular OCT Scan of Patient 1 (OS) After Discontinuation of Latanoprost (2/15/2007), Showing CME Resolution with a Retinal Thickness of 164μm.

Macular OCT Scan (OS) of Patient 1 Following Latanoprost Re-Administration (3/8/2007), Showing CME Recurrence with a Retinal Thickness of 408μm.

Figure 3. Macular OCT Scan (OS) of Patient 1 Following Latanoprost Re-Administration (3/8/2007), Showing CME Recurrence with a Retinal Thickness of 408μm.

Macular OCT Scan of the Same Patient (OS) Following Discontinuation of Latanoprost (4/10/2007), Showing CME Resolution with a Retinal Thickness of 140μm.

Figure 4. Macular OCT Scan of the Same Patient (OS) Following Discontinuation of Latanoprost (4/10/2007), Showing CME Resolution with a Retinal Thickness of 140μm.

Case 2

A 75-year-old man presented with blurred vision OD, 3 weeks following ipsilateral phacoemulcification. No history of systemic conditions, including diabetes mellitus, was reported. Ophthalmic history was significant for pseudoexfoliative glaucoma OU, under treatment with latanoprost for the last 7 years. No other medications were systematically used in either eye whereas a 6-week course of combined tobramycin–dexamethazone regimen in a tapering fashion had been used OD following cataract extraction. Furthermore, no history of uveitis or vitreoretinal disorders was reported. Zonular instability was not detected preoperatively. The surgery was uncomplicated. Mechanical stretching of the iris was used to augment mydriasis intraoperatively whereas the total operating time was 37 minute. The IOL implanted in the capsular bag was a 22.5 D AcrySof ® Natural (Alcon, Fort Worth, TX).

Upon presentation, BCVA was 20/32 (OD) and 20/25 (OS). Biomicroscopy of the anterior segment was significant for conjunctival hyperemia and pseudoexfoliative material on the pupillary rim (OU). Funduscopy OD was significant for mild macular elevation. Fluorescein angiography and OCT scan confirmed the presence of CME OD. Latanoprost was discontinued OD and replaced by timolol–dorzolamide bid. Topical ketorolac qid was also administered. Three weeks later, BCVA was 20/20 OD and a new OCT scan confirmed the resolution of CME.

Case 3

An 82-year-old woman presented for a routine postoperative examination 1 month following phacoemulcification surgery OS. Systemic history was significant for coronary artery disease and arterial hypertension. However, no history diabetes mellitus was reported. Ophthalmic history was significant for pseudoexfoliative glaucoma OS, diagnosed 2 years before, under treatment with latanoprost. No other medications were systematically used in either eye whereas a 6-week course of combined tobramycin–dexametha-zone regimen in a tapering fashion had been used OS following cataract extraction. No history of uveitis or vitreoretinal disorders was reported. Zonular instability was not detected preoperatively. The surgery was uncomplicated. Intraoperative mechanical stretching of the iris to augment pharamacological mydriasis was performed whereas the total operating time was 31 minute. The IOL implanted in the capsular bag was a 21D AcrySof® Natural (Alcon, Fort Worth, TX)

Upon presentation, BCVA was 20/40 (OS) and 20/32 (OD). Conjunctival hyperemia was noted OU. Biomicroscopy revealed pseudoexfoliative material on the pupillary rim (OU) as well as the anterior capsular bag (OD). Fundoscopy OS was significant for retinal edema and irregular foveal reflex. Fluorescein angiography and OCT scan confirmed the presence of CME. Latanoprost was then discontinued, OS, replaced by Timolol bid. Ketorolac eye drops qid were also administered OS. Three weeks later, BCVA OS had improved to 20/25, whereas a new OCT scan confirmed the resolution of the CME.

Discussion

CME associated with latanoprost has been reported after complicated cataract surgery, by several previous studies.1,6,7 In most cases reported, risk factors (such as uveitis, epiretinal membrane, vein occlusion, uveitis, intraoperative vitreous loss, or YAG-laser posterior capsulotomy) were present. A previous study has also reported the occurrence of clinically significant CME following uncomplicated phacoemulcification in eyes receiving latanoprost.8 In that report, CME diagnosis was based on characteristic clinical findings of ocular fundus examination whereas eyes with PEX had been excluded.8 This study presents a series of 3 glaucomatous patients who developed OCT-proven CME within months following uncomplicated phacoemulcification in eyes with PEX. None of the patients had significant risk factors for CME development whereas the association with latanoprost use is strongly indicated by the fact that a complete resolution of the CME was noted following discontinuation of latanoprost whereas, in one case, a recurrence of CME was noted immediately following latanoprost re-administration. These findings imply that a causal relationship between topical latanoprost and CME may exist.

Although the precise pathogenesis of postoperative CME is not yet fully understood, several studies have proposed that a disruption of the blood–retinal barrier may play a key role.3,7 The fact that anti-inflammatory agents suppressing prostaglandin synthesis may affect the clinical course of the condition implies that prostaglandins play a role in CME pathgenesis.3,7 Latanoprost has not been shown to be vasoactive even at concentrations well above those used therapeutically, although many naturally occurring prostaglandins have vasoactive properties.7 Nevertheless, a disruption of blood–aqueous barrier and associated anterior chamber inflammation has been described following latanoprost administration in human eyes.9 Undoubtedly, the number of eyes developing CME (described in published reports) is very small in comparison with the number of eyes treated with latanoprost worldwide.7 However, the described cases of latanoprost-dependent CME following uncomplicated cataract surgery imply that some patients may have an increased susceptibility to disruption of the blood–retinal barrier in response to latanoprost. Patients presented in this report shared some similarities concerning clinical findings, including conjunctival hyperemia (attributed to latanoprost use), advanced age and long term history of latanoprost use prior to cataract extraction. Interestingly, all patients also had PEX at the affected eyes. A previous study examining risk factors for CME development following phacoemulcification did not detect a statistically significant association between PEX and CME.10 However, the frequent need to mechanically stretch the iris in order to overcome the PEX-related deficient pharmacological mydriasis may be associated with iris trauma, prolonged surgical time and increased levels of postoperative inflammation. Furthermore, a dysfunction of blood–aqueous barrier has been previously described in eyes with PEX,11 which may possibly be enhanced by the concomitant use of latanoprost. It has also been previously proposed that severe conjunctival hyperemia associated with the use of latanoprost may be an indication of predisposition to the development of CME following cataract surgery.5 Therefore, specific clinical findings, such as PEX or latanoprost-related conjunctival hyperemia, may possibly be used as indicators of increased susceptibility to the effects of prostaglandins. Previous studies have suggested that the response to latanoprost varies between individuals, possibly due to polymorphisms to F2a receptor gene.12 The retrospective nature and small number of cases limit the strength of this study, especially since the possibility of spontaneous resolution of pseudophakic CME is well documented in previous reports.13 Future prospective trials may aim at detecting patients at risk for developing CME associated with latanoprost or other prostaglandin analogues, based on molecular genetic information or on clinical findings, and thus may lead to establishing specific contra-indications for prostaglandin use following cataract surgery.

References

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  13. Price FW Jr, Whitson WE. Natural history of cystoid macular edema in pseudophakic bullous keratopathy. J Cataract Refract Surg. 1990;16:163–169.
Authors

From the Department of Ophthalmology, University Hospital of Heraklion, Crete, Greece.

The authors have no financial or proprietary interest in the materials presented herein.

Address correspondence to Efstathios T. Detorakis, MD, PhD, Department of Ophthalmology University Hospital of Heraklion, 71110, Heraklion, Crete, Greece.

10.3928/15428877-20100215-91

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