Correspondence Our modeling has presented LCS CEA in what we believe may be a realistic possible benefit, but recognizing that benefits may be lesser or greater than this, also modeled those scenarios. Although we indicated in the text “personal experience,” this does not mean unpublisheddwe should highlight our assumption of 5% visual benefit reflects our (early) published data, which we have already indicated would require sample size of n > 1500 to show significance.2 In the absence of prospective, randomized, controlled trial evidence (evidence the FEMCAT study hopefully will address), we have presented findings based on the first published, prospective, single-center and multicenter, comparative, cohort study findings.3,4 Reanalysis of our CEA modeling adjusting for potential increased complications associated with LCS would demonstrate that LCS is even less cost effective than we modeled.3 Many surgeons could validly consider LCS as “regression to the mean” for intra- and intersurgeon variability in outcomes compared with PCS. By convention, current measurement of cost per QALY (the overall utility of vision for patients) is driven by their better seeing eye achieving 6/12 (20/40), and when analyzing cost per QALY gained, improvement in the worse eye does not add significantly to that obtained by the better eye. Furthermore, the incremental benefit in QALY gains between 6/12 and 6/6 is significantly less than the gain to 6/12. Although additional cost-effectiveness gains may be associated with improving patients to 6/6 or 6/9 from 6/12, the magnitude of these will be negligible, given that 6/12 is already near the ceiling of “quality-oflife” outcomes. That is not to say that these higher level outcomes will not have perceived benefit for patients, but rather that, in quality-of-life terms, they can ultimately only be up to the level of perfection (1.0). As our modeling indicated, even if perfect outcomes are obtained, LCS is not cost effective at current cost to patients. A reduction in cost to patient may bring this technology within accepted cost-effectiveness standards (and yet would remain 6-fold less cost-effective than our existing PCS). We therefore disagree that our modeling does not allow economic modeling of fees. LCS has a real cost. Even if it provides perfect outcomes, its current cost to patient is too great. Our calculations suggest that LCS needs to be priced at less than $300 to $500 (cost to patient) to come close to being cost effective. We agree that a probabilistic sensitivity analysis based on data from a randomized, controlled trial such as the FEMCAT study will only better inform us with regard to the incremental cost effectiveness ratio cost per QALY gained for LCS. It is important to note that the 2 procedures being compared are not independent of each other and thus a deterministic sensitivity analysis remains an important method in that context.5 We congratulate the FEMCAT study group and the French Ministry of Health for embarking on their large, multicenter, randomized, controlled trial. Such studies certainly are essential. The time for presentation of retrospective, noncomparative series has passed. Higher level evidence, such as our comparative cohort studies (level III) and randomized control trials (level II) such as the FEMCAT study, are required. Our analysis provides clear floor and ceiling levels for surgeons to measure the cost effectiveness of this technology scientifically rather than as marketed claims.
SHAUN Y.P. EWE, MBBS ROBIN G. ABELL, MBBS BRENDAN J. VOTE, FRANZCO Tasmanian Eye Institute, Launceston, Tasmania, Australia
References 1. Abell RG, Vote BJ. Cost-effectiveness of femtosecond laserassisted cataract surgery versus phacoemulsification cataract surgery. Ophthalmology 2014;121:10–6. 2. Abell RG, Kerr NM, Vote BJ. Towards zero effective phacoemulsification time using femtosecond laser pretreatment. Ophthalmology 2013;120:942–8. 3. Abell RG, Davies PE, Phelan D, et al. Anterior capsulotomy integrity after femtosecond laser-assisted cataract surgery. Ophthalmology 2014;121:17–24. 4. Abell RG, Kerr NM, Vote BJ. Femtosecond laser-assisted cataract surgery compared with conventional cataract surgery. Clin Exp Ophthal 2012;41:455–62. 5. Briggs AH, Weinstein MC, Fenwick EAL, et al. Model parameter estimation and uncertainty: a report of the ISPORSMDM modeling good research practices task force-6. Value In Health 2012;15:835–42.
Re: Afshar et al.: Dexamethasone intravitreal implant trapped at the macula in a silicone oil-filled eye (Ophthalmology 2013;120:2748-9) Dear Editor: We read with interest the article entitled “Dexamethasone intravitreal implant trapped at the macula in a silicone oil-filled eye,”1 in which the authors report the first case of the preparation becoming trapped against the retinal surface. Afshar et al1 describe epiretinal membrane formation presumed secondary to the implant’s anomalous position and advocate either its prompt surgical removal or an attempt to displace the implant through posturing. We wish to share our experience where an implant also became trapped in the premacular region, but with a markedly different outcome. This may help the reader to adopt a balanced approach if faced with this clinical scenario. A 38-year-old, highly myopic man required surgery for a recurrent rhegmatogenous retinal detachment complicated with proliferative vitreoretinopathy. Dexamethasone (Ozurdex, Allergan, Irvine, CA) was injected into his silicone oil-filled eye as part of a randomized, controlled clinical trial investigating its effect on complicated retinal detachments.2 The implant was administered through an open sclerostomy as per study protocol. At 10 days postoperatively, the intact implant was observed trapped behind the oil bubble within the retinal arcades at the edge of a posterior staphyloma with a good oil-fill recorded. At 30 days postoperatively, the implant had spontaneously fractured into 2 pieces. Spectralis-domain optical coherence tomography performed over the larger fragment confirmed its position in apposition to the retina and posterior to the oil meniscus (Figs 1-2). One month later, both fragments had spontaneously relocated to the vitreous base without any adverse effect noted on the retinal surface. The patient subsequently underwent routine combined removal of silicone oil and cataract extraction with posterior chamber intraocular lens implantation, 8 weeks later. The retina remains attached 2 months after oil removal without any observed negative sequelae from the initial anomalous implant position. The presence of a trapped dexamethasone implant at the posterior pole may indeed be an alarming observation, and on the strength of the findings reported by Afshar et al alone, may initially
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Ophthalmology Volume 121, Number 10, October 2014
Figure 1. A, Infrared image of dexamethasone implant trapped at posterior pole on edge of posterior staphyloma (arrow) in oil-filled eye at day 10 postoperative visit. B, Infrared image of sponatenously fractured dexamethasone implant at day 30 postoperative visit.
trigger concern. However, we did not observe any negative effects of this eventuality in our case. In particular, no associated epiretinal membrane formation was noted over a 6-month period after implant administration, which was confirmed on serial, sequential spectralis domain optical coherence tomography assessment. We acknowledge that it may be difficult to draw direct comparisons between the 2 cases owing to the differing contexts in which the product was used. First, the timing of implant administration and oil injection differ, with the former preceding the latter by 2 weeks in Afshar et al’s report. This may have allowed additional matrix degradation time and perhaps an alteration in the surface properties of the product. Second, the amblyopic nature of our patient may have limited reporting of visual symptoms, particularly because the implant was initially positioned over an area of marked myopic chorioretinal atrophy. Finally, the duration of time over which the implant was apposed to the retinal surface differ. The fractured implant spontaneously relocated to the vitreous base between 4 and 8 weeks post injection, whereas Afshar et al first observed epiretinal membrane formation at 2 months.
Additionally, our case highlights an unreported phenomenon; although fractured implants directly related to the injection process have been previously reported,3e5 its delayed occurrence has not previously been observed. The presence of a significant posterior staphyloma and the use of silicone oil may, in part, explain this; the implant was seen trapped at the edge of the staphyloma at day ten post injection. We hypothesize that the buoyancy force of the silicone oil on the implant over the edge of the staphyloma may have precipitated its delayed fracture (an analogy being the snapping of a pencil over the edge of a table). Our case challenges the suggestion reported by Afshar et al that the retinaleoil interface is not a dynamic environment, because the spontaneous relocation of the previously trapped implant, in our opinion, refutes this. We also question the need for prompt invasive intervention; although a trapped implant under oil at the macula is alarming, in our case it seems to have been an innocuous finding. Nevertheless, we agree that further reports are warranted, to estimate its incidence and help to guide clinical decisions as to whether or not the risk/benefit ratio is in favor of prompt operative intervention.
Figure 2. Spectralis domain optical coherence tomography highlighting fragmented dexamethasone implant postioned posterior to silicone oil meniscus (arrow) and in apposition to retinal surface.
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Correspondence PHILIP JAMES BANERJEE, BMEDSCI, FRCOPHTH PETROS PETROU, MD DAVID G. CHARTERIS, FRCSED, FRCOPHTH Vitreoretinal Service, Moorfields Eye Hospital, London, UK Financial disclosure(s): Allergan, Ireland, provided the funding for the randomized, controlled trial in which the patient was a participant.
References 1. Afshar AR, Loh AR, Pongsachareonnont P, et al. Dexamethasone intravitreal implant trapped at the macula in a silicone oil-filled eye. Ophthalmology 2013;120:2748–9. 2. Banerjee PJ, Bunce C, Charteris DG. Ozurdex(R) (a slowrelease dexamethasone implant) in proliferative vitreoretinopathy: study protocol for a randomised controlled trial. Trials 2013;14:358. 3. Rishi P, Mathur G, Rishi E. Fractured Ozurdex implant in the vitreous cavity. Indian J Ophthalmol 2012;60:337–8. 4. Roy R, Hegde S. Split Ozurdex implant: a caution. Can J Ophthalmol 2013;48:e15–6. 5. Agrawal R, Fernandez-Sanz G, Bala S, Addison PK. Desegmentation of Ozurdex implant in vitreous cavity: report of two cases. Br J Ophthalmol 2014;98:961–3.
Author reply Dear Editor: We read with interest the case reported by Banerjee et al of a dexamethasone implant trapped under silicone oil at the macula in a myopic young man, and the delayed fracture of the implant. Banerjee et al challenge our assertion1 that the retinal/silicone oil interface is not a dynamic environment, citing the spontaneous relocation of the trapped implant in their case. However, the presence of a significant posterior staphyloma in their case alters the retinaleoil interface. Specifically, a staphylomatous eye filled with silicone oil will have an aqueous phase at the bottom of the eye, and a second aqueous phase layering at the bottom of the staphyloma. To test this hypothesis, a model eye was constructed in the laboratory. Two 5/8-inch diameter clear, acrylic half spheres (Kit Kraft, Los Angeles, CA) were glued together with a solvent based adhesive to create a model globe. A drill was used to create a 7/16-inch diameter opening in the posterior pole of the sphere. A 7/16-inch diameter half sphere was attached to the back of the model globe with adhesive, to simulate a posterior staphyloma. Holes were drilled through the top of the model for access. Indocyanine green was mixed with aqueous solvent and injected in the bottom of the model eye to simulate an aqueous phase. Silicone oil 5000 Centistokes (Alcon Laboratories, Fort Worth, TX) was injected over the indocyanine green to fill the model. A highresolution photograph (Fig 1) was taken with a camera attachment on an operating microscope that was tilted 90 (Lumera, Carl Zeiss Meditech, Jena, Germany). The model confirms the presence of an aqueous phase at the bottom of the globe and a second aqueous phase at the bottom of the staphyloma in a silicone oil-filled eye. In the case reported by Banerjee et al, the implant was trapped at the bottom edge of the posterior staphyloma, in the aqueous phase of the staphyloma. This location is more dynamic than the oil phase above. This could explain migration of the implant. In addition, the presence of the implant in this aqueous phase, with associated
Figure 1. An acrylic model eye with posterior staphyloma, filled with indocyanine green to highlight the aqueous phase and silicone oil 5000 Centistokes. Note aqueous phase formation is seen at both bottom of the globe and bottom of the staphyloma.
increased mobility, could have caused repetitive microtrauma against the staphyloma edge, contributing to fracture. We agree that further study is warranted.
ARMIN R. AFSHAR, MD, MBA JAY M. STEWART, MD Department of Ophthalmology, University of California, San Francisco, San Francisco, California
Reference 1. Afshar AR, Loh AR, Pongsachareonnont P, Schwartz, et al. Dexamethasone intravitreal implant trapped at the macula in a silicone oil-filled eye. Ophthalmology 2013;120:2748–2749.e1.
Re: Levy-Clarke et al.: Expert panel recommendations for the use of anti-tumor necrosis factor biologic agents in patients with ocular inflammatory disorders (Ophthalmology 2014;121:785-96) Dear Editor: We read with great interest the article by Levy-Clarke et al1 reporting the recommendations of an expert panel for the use of anti-tumor necrosis factor (anti-TNF) a agents in patients with ocular inflammatory diseases. Based on systematic review of published data, the authors endorse the use of infliximab and adalimumab as a first-line immunomodulatory agent for the treatment of Behçet’s uveitis, a potentially blinding disease. Behçet’s uveitis is the most common form of uveitis in tertiary eye care centers in Turkey.2 Patients with posterior segment involvement are initially treated with corticosteroids combined with azathioprine and/or cyclosporine. We use biologic agents as second-line therapy, and interferon alfa is given as the first-choice biologic agent. If relapses
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