Internal limiting membrane peeling

Internal limiting membrane peeling

Letters to the Editor Biostatistics Dear Editor: The guest editorial on biostatistical education in ophthalmology is most timely and appropriate.1 Con...

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Letters to the Editor Biostatistics Dear Editor: The guest editorial on biostatistical education in ophthalmology is most timely and appropriate.1 Considering the current technical and information explosion in ophthalmology, critical appraisal of an article before using the information in clinical practice is perhaps even more crucial in developing countries. I entirely agree with Dr Cox about the need for biostatistical education during residencies, but feel that actual interpretation and application of the published literature require slightly expanded skills. These skills are provided by a basic knowledge of clinical epidemiology, which is essentially a commonsense approach to medicine2 and is the mother of evidence-based medicine. The way I was taught clinical epidemiology, concepts behind statistics were more important than the actual calculations, which, bar a few simple ones, were really not considered necessary to understand, interpret, or apply the literature. This was fortunate, because the few calculations taught were actually simple enough to be learnt by a selfconfessed numerophobe like myself. Instead of actually knowing formulas, understanding what was required and the ability to look that up were considered more desirable. In this context, provided the 42 ophthalmologists who were informally quizzed by Dr Cox understood the need to know the sensitivity, specificity, and predictive values and were able to find the required formulas, they were probably okay. It is also my personal opinion that an understanding of and analysis using the humble 2⫻2 table are probably of more value than many formulas. As far as the teaching of skills is concerned, again I cannot agree more with Dr Cox. To the best of my knowledge, only 1 of the 100 or more ophthalmology residency programs in India actually taught clinical epidemiology formally and insisted on its application in day-to-day clinical practice (past tense intended). In my current location, the skills are taught in a manner similar to what Dr Cox has suggested. Fellows participate in interactive introductory sessions on all the concepts Dr Cox mentions (and more). Although the concept and some basic calculations involved in statistical tests and significance are ably taught by our biostatisticians, the emphasis is on an appreciation of clinical significance using concepts like the number needed to treat.3 Fellows are formally taught critical appraisal of articles, and this is reinforced during subsequent journal club presentations. Appraisal and clinical epidemiology skills are further refined during case presentations in which evidence is required for all actions. The basic resource text used in our program is Sackett et al’s Clinical Epidemiology.2 Although not directly related to ophthalmology, it certainly simplifies concepts and is easy reading to boot. Books on evidence-based medicine and users’ guides to the medical literature are additional resources. As far as journal articles are concerned, initially, at

least, we insist on the format provided by Riegelman in Studying a Study and Testing a Test.4 The program in our institute has been in place for the last couple of years. When we recently tested fellows’ knowledge in this arena (questions included all the concepts Dr Cox referred to as essential), all fellows scored over 80%. The examination was open book, and I make no excuses: the ability to find the answers is an essential of the philosophy. As the word biostatistics itself is likely to put off most ophthalmologists, we call our module “a common sense approach to ophthalmology.” Our biostatisticians and clinicians participate in the teaching/learning process. The deficiencies are that class and journal clubs start at 7 AM, and breakfast is not served. There is a definite need to make commonsense ophthalmology more attractive; after reading the editorial, I am considering moving our sessions to an evening with food and further discussions at the pub next door. RAVI THOMAS Hyderabad, India References 1. Cox TA. Biostatistical education in ophthalmology. Ophthalmology 2004;111:209 –10. 2. Sackett D, Haynes RB, Guyatt GH, Tugwell P. Clinical Epidemiology: A Basic Science for Clinical Medicine. 2nd ed. Boston: Little Brown; 1991. 3. Thomas R, Padma P, Braganza A, Muliyil J. Assessment of clinical significance: the number needed to treat. Indian J Ophthalmol 1996;44:113–5. 4. Riegelman RK. Studying a Study and Testing a Test. How to Read the Medical Evidence. Philadelphia: Lippincott, Williams and Wilkins; 2000.

Internal Limiting Membrane Peeling Dear Editor: With great interest we read the article by Dr Wolf et al1 describing the ultrastructural effects of internal limiting membrane (ILM) peeling in a human donor eye. We congratulate the authors on the excellent histological sections presented in their article, which allow impressive insights into retinal morphology after indocyanine green (ICG)– assisted peeling of the ILM. Obviously, an important aspect of this article is the short postmortem time the eyes were obtained. As a consequence, the authors were able to provide the histology of fresh tissue with negligible postmortem artifacts. This is of special importance, as previous studies described morphological effects of ICG on the retina in eyes with longer postmortem times.2 Other authors attributed these morphological alterations of the retina to the prolonged postmortem time and the vitality of the tissue.3 There is one aspect of the ultrastructural findings that is not discussed in the present report, and we would be very interested to learn about the authors’ opinion on this point: the histology of the control eye as shown in Figure 1 provides very well-preserved tissue, with no signs of arti-

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Ophthalmology Volume 111, Number 9, September 2004 facts indicating autolysis; there is no vacuolization and no damage to Müller cell endfeet. In the ICG-treated eye, the findings are very different: looking at the histology of the nonpeeled area of the eye in which ICG was used for ILM staining, some Müller cell endfeet appear swollen, with reduced electron density; in the transition zone, cellular damage was more pronounced, with the appearance of empty spaces containing cellular debris and damaged Müller cell endfeet, which were also seen in the peeled area of the retina. We recently discussed the impact of ICG on the morphology of the vitreoretinal interface using a different experimental approach.2,4 We found detachment of the ILM and disruption of Müller cells after ICG staining without illumination or ILM peeling. Gross disorganization of the inner retina was seen after ICG staining with subsequent illumination beyond 620 nm. In our experience, it is not clear from the present experimental setting whether the ultrastructural findings of ruptured Müller cells adherent to the retinal side of the ILM are more likely to be caused by staining of the ILM using ICG or by mechanical forces induced during ILM peeling. Could the authors please comment on a possible impact of ICG itself that might have contributed to the histological findings presented in their article? In addition, it would have been worthwhile to present the histology of the retina after ILM peeling without ICG assistance. At present, we should be careful to draw any definite conclusions on the potential damaging effect of conventional ILM peeling based on the study design presented. CHRISTOS HARITOGLOU, MD ARND GANDORFER, MD ANSELM KAMPIK, MD Munich, Germany References 1. Wolf S, Schnurbusch U, Wiedemann P, et al. Peeling of the basal membrane in the human retina: ultrastructural effects. Ophthalmology 2004;111:238 – 43. 2. Gandorfer A, Haritoglou C, Gandorfer A, Kampik A. Retinal damage from indocyanine green in experimental macular surgery. Invest Ophthalmol Vis Sci 2003;44:316 –23. 3. Grisanti S, Szurman P, Gelisken F, et al. Histological findings in experimental macular surgery with indocyanine green. Invest Ophthalmol Vis Sci 2004;45:282– 6. 4. Haritoglou C, Gandorfer A, Gass CA, Kampik A. Histology of the vitreoretinal interface after staining of the internal limiting membrane using glucose 5% diluted indocyanine and infracyanine green. Am J Ophthalmol 2004;137:345– 8.

Author reply Dear Editor: Haritoglou et al have raised a very important question regarding the effects of indocynanine green (ICG) on the integrity of the Müller cell endfoot–ILM interface (and the inner retina) after staining with ICG. They had observed ILM detachment and disruption of Müller cells after ICG staining in postmortem eyes with postmortem times of 16 to 30 hours.1 In our study, we observed no detachment of the ILM and

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Figure 1. A human postmortem eye after experimental peeling.2 A, Light microcopy of a semithin section, showing the transition (arrow) between the peeled area (right side) and the nonpeeled area. The circle labels an area corresponding to that shown in B. B, Transmission electron microcopy of the inner retina close to— but outside—the peeled area. There is no detachment between the basal lamina (BL) and the Müller cell endfeet (MC); the latter appear as intact as the axons (AX) of retinal ganglion cells. C, Intraoperative visualization of ICG applied (and illuminated) across the entire macular area.

no abnormalities of the ILM–Müller cell endfeet interface in areas remote from the peeled area (Fig 1A, left side). The Müller endfeet and the inner retina appeared normal, even in areas close to the peeled area (Fig 1B). Because we have ICG-stained and illuminated the whole macular area (Fig