Letters to the Editor

3. Pardo-Lopez D, Frances-Muñoz E, Gallego-Pinazo R, Diaz-Llopis M. Anterior chamber migration of dexamethasone intravitrealimplant. Graefes Arch Clin Exp Ophthalmol 2011 Aug 23 [Epub ahead of print].

4. Yeh WS, Haller JA, Lanzetta P, et al. Effect of the duration of macular edema on clinical outcomes in retinal vein occlusion treatedwith dexamethasone intravitreal implant. Ophthalmology 2012;119:1190–8.

Author reply

Dear Editor:We thank Drs Garay-Aramburu and Cabrerizo for their commentary on our paper “Dexamethasone intravitreal implant in patients withmacular edema related to branch or central retinal vein occlusion twelve-month study results”1 and are pleased that their experiencedovetails with our findings that the dexamethasone intravitreal implant is effective. We also congratulate them on the optical coherencetomography study that showed significant closure of the 22-gauge scleral tunnel at day 1 and complete closure at day 7. These findingscorrespond nicely with those reported by Taban et al,2 who also demonstrated with optical coherence tomography complete closure ofsclerotomy wounds by day 1 when using a 23-gauge sclerotomy microincision and an oblique approach.

Although the authors believe that a 2-step, biplanar injection technique is important, and it is interesting to read their thoughts, we know ofno clinical evidence that the injection method can impact safety or efficacy. An injection technique that uses an oblique incision may be morevaluable in an animal model,3 but clinical experience has not borne out a difference in outcomes. The dexamethasone implant has been used forthe treatment of macular edema due to branch and central retinal vein occlusions since its approval in June 2009. Thousands of patients with retinalvein occlusion have received the implant, many with repeat injections. The authors themselves, on systematic literature search, found no reportsdescribing complications such as scleral leaks, choroidal detachment, or vitreous prolapse owing to the injection technique. We also found no suchreports of complications or problems related to the injection procedure in our prospective clinical trial (n � 1256).1

Indeed, this type of debate regarding sclerotomy architecture was prevalent in the early days of sutureless vitrectomy surgery, butbiplanarity never was found to be critical as long as a component of the scleral incision was oriented obliquely to the eye wall, rather thanhaving an entirely perpendicular entry. A wound or injection technique with an oblique component was also shown to be more valuablein an animal model than a straight incision for sutureless vitrectomy in preventing wound leakage, hypotony, and endophthalmitis.3

The results of the GENEVA study1 demonstrated that, for the majority of patients, dexamethasone intravitreal injections can be repeatedwith no new safety concerns after a second injection. Among patients with macular edema secondary to branch retinal vein occlusion orcentral retinal vein occlusion, single,4 and more critically, repeated treatment1 with dexamethasone implants had a favorable safety profileover 12 months. In patients who received 2 intravitreal dexamethasone injections, the efficacy and safety of the 2 implants were similarwith the exception of cataract progression. We have not seen serious sclerotomy-related adverse events from any registration trial even aftermultiple injections (data not shown).

JULIA A. HALLER, MD,1 FRANCISCO BANDELLO, MD,2 RUBENS BELFORT, JR, MD,3 MARK GILLIES, MD,4

ANAT LOEWENSTEIN, MD,5 YOUNG HEE YOON, MD,6 XIAO-YAN LI, MD,7 SCOTT M. WHITCUP, MD7

1Wills Eye Institute, Philadelphia, Pennsylvania; 2University Vita Salute, Hospital San Raffaele, Milan, Italy; 3Vision Institute, Federal University ofSao Paulo, Sao Paulo, Brazil; 4University of Sydney, Sydney, Australia; 5Tel Aviv Medical Center, Tel Aviv, Israel; 6Asan Medical Center, Seoul,Korea; 7Allergan, Inc., Irvine, California; for the Ozurdex GENEVA Study Group

References

1. Haller JA, Bandello F, Belfort R, Jr, et al. Dexamethasone intravitreal implant in patients with macular edema related to branch orcentral retinal vein occlusion twelve-month study results. Ophthalmology 2011;118:2453–60.

2. Taban M, Sharma S, Ventura AA, Kaiser PK. Evaluation of wound closure in oblique 23-gauge sutureless sclerotomies with Visanteoptical coherence tomography. Am J Ophthalmol 2009;147:101–7.

3. Taban M, Ventura AA, Sharma S, Kaiser PK. Dynamic evaluation of sutureless vitrectomy wounds: an optical coherence tomographyand histopathology study. Ophthalmology 2008;115:2221–8.

4. Haller J, Bandello F, Belfort R Jr, et al. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients withmacular edema due to retinal vein occlusion. Ophthalmology 2010;117:1134–46.

Geographic Location and Endophthalmitis

Dear Editor:Keay et al1 reported the postoperative endophthalmitis (PE) incidence after cataract surgery in 48 of the states of the United States. TheUS incidence decreased from 1.33 cases per 1000 surgeries in 2003 to 1.11 in 2004. Also, male gender, age �85 years, black race, NativeAmericans, and surgery performed by surgeons with low annual volume or less experience had increased rates.1 Possible stronger riskfactors such as the prophylaxis practices and the surgical technique cannot be assessed.1 However, it is known that the intracameralantibiotic prophylaxis was unusual in the United States2 before 2007. During the study period,1 in Europe, without using intracameralprophylaxis, the PE incidence was 3.26 and 2.51 cases per 1000 surgeries in groups A and C of the European Society of Cataract andRefractive Surgeons study,3 respectively. The different contemporary incidence in the United States and Europe suggests the influence ofother factors such as the geographic location.

Keay et al1 reported an adjusted incidence range from 0.81 in a northern state (Idaho) to 2.62 in a southern state (Missouri) mean value,

1.57. This range was arbitrarily stratified into 6 levels, which they summarized on a map. Keay et al suggest that climate does not influence

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PE rates. Each of their 4 central levels comprises a narrow range of about 0.25 PE cases per 1000 operations. The PE rate variation from2003 to 2004 by itself accounted for 0.22 and they suggest improvements in the surgical wound construction and changes in surgicaltechniques and prophylaxis as being responsible for this annual variation. For instance, a recent study conducted in one of the states4

reported a lowering of incidence of severe adverse events after cataract operations (including PE) from 1994 to 2006 and attributed thisdecrease to technologic innovations in phacoemulsification machines, instruments available to manage complex cases (pupil stretchers,capsular tension rings, and dyes to stain the capsule), an increase in topical anesthesia use, improvements in intraocular lenses, changesin operative medication, and better strategies for dealing with intraoperative complications.

A different view of a possible geographical influence on PE would be obtained if the adjusted PE rates range were stratified into 3 levels,taking as the central level their interquartile range (1.43–1.71). Thus, most of the 23 states having a rate within this range would be locatedin the central geographical area. With a PE rate of �1.43, there would be 13 states, and 11 would be located in the north. With an incidence�1.71, there would be 12 states and 7 would be located in the south (Fig 1, available at http://aaojournal.org).

To reinforce the possible influence of the geographical location on the PE rates, we have gathered the published PE incidences of 15European countries, selecting surgeries from 1981 to 2005, before the systematic use of intracameral antibiotic prophylaxis. After 857 315cataract operations, there were 1504 PE cases. The mean incidence was 1.75 PE cases per 1000 surgeries, ranging from 1.15 to 8.40,showing a clear increase from north to south (Table 1 and Fig 2, available at http://aaojournal.org).

We hypothesize the geographic location could influence PE incidence in 2 ways: The depressed socioeconomic status sometimesassociated with harder climatic conditions and variation of conjunctival bacteria prevalence of patients operated on owing to the climate.5

Both factors seem to change in parallel in the 15 European countries from north to south, but this tendency seems to be less apparent inthe US data set, with different climates (Arizona, New Mexico) and richer (New Hampshire) and poorer (Montana) States in the samelatitude (Fig 3; and Table 2, available at http://aaojournal.org). It is our perception that intracameral prophylaxis minimizes the PE incidencevariation among European countries. However, growing bacterial antibiotic resistance could change this situation and a deeper knowledgeof the conjunctival bacteria variation would be needed to improve prophylaxis.

MARÍA ELISA FERNÁNDEZ-RUBIO, PHDGregorio Marañón, University General Hospital, Madrid, Spain.

References

1. Keay L, Gower EW, Cassard SD, et al. Postcataract surgery endophthalmitis in the United States. Analysis of the Complete 2003 to2004 Medicare database of cataract surgeries. Ophthalmology 2012;119:914–23.

2. Chang DF, Braga-Mele R, Mamalis N, et al; ASCRS Cataract Clinical Committee. Prophylaxis of postoperative endophthalmitis aftercataract surgery: results of the 2007 ASCRS member survey. J Cataract Refract Surg 2007;33:1801–5.

3. Endophthalmitis Study Group, European Society of Cataract & Refractive Surgeons. Prophylaxis of postoperative endophthalmitisfollowing cataract surgery: results of the ESCRS multicenter study and identification of risk factors. J Cataract Refract Surg2007;33:978–88.

4. Stein JD, Grossman DS, Mundy KM, et al. Severe adverse events after cataract surgery among Medicare beneficiaries. Ophthalmology2011;118:1716–23.

5. Rubio EF. Climatic influence on conjunctival bacteria of patients undergoing cataract surgery. Eye 2004;18:778–84.

Author reply

Dear Editor:Dr Elisa’s analysis1 provides a thought-provoking question regarding the potential association between climate (defined by latitude) and the rateof postoperative endophthalmitis. The potential relationship between geography/climate and postoperative endophthalmitis is one that has beenof interest in many settings; however, to our knowledge, evidence of a relationship is extremely limited. The south–north gradient in Dr Elisa’sversion of the rates in the United States (US) show substantially more variation than the south–north gradient in the European map. In the US,both extreme northern and extreme southern states fall into the highest category: Montana, Wyoming, and Florida. Similarly, some of the southernstates—Arkansas and New Mexico—fall into the lowest rate category, and some of the northern states fall into the middle category.

Within the 15 countries of Europe included in Dr Elisa’s analysis, substantial variation exists in socioeconomic status, culture, diet,ethnicity, health systems, and related practice. Thus, many important confounders likely cannot be accounted for in this analysis. One mayquestion whether the south to north gradient in the US means the same thing as it does in Europe. We believe it does not, given that theUS does not have the same diversity in healthcare systems and cultures across this gradient. Unfortunately, the types of data available forboth our study and Dr Elisa’s do not provide the details to be able to further investigate this question. In addition, to make a more faircomparison, it would be useful to follow the same methodology for both figures—either to use the same 3 cutpoints from the US figurefor the European figure, or to have below, within, and above the interquartile range for Europe for the European figure.

We recognize the possibility that pathogens likely vary by region and also by temperature. To this end, within our original analyses,2

we explored the possible relationship between endophthalmitis rate and seasonality, with the hypothesis that endophthalmitis would bemore common in warmer months. However, we did not find an association between season and endophthalmitis rate. To our knowledge,Li et al are the only group that has demonstrated a statistically significant association between season and postoperative endophthalmitis.In their study of cataract surgeries performed in Western Australia, they found that surgeries performed in the winter carried a 48%increased risk of endophthalmitis compared with surgeries performed in the spring (odds ratio, 1.48; 95% confidence interval, 1.00–2.18).

Summer and autumn had somewhat higher rates than spring, but the difference was not significant.3

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Figure 1. Adjusted endophthalmitis rates per 1000 cataract surgeries in t

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References

1. Verbraeken H. Treatment of postoperative endophthalmitis. Ophthalmologica 1995;209:165–71.2. Norregaard JC, Thoning H, Bernth-Petersen P, et al. Risk of endophthalmitis after cataract extraction: results from the international

cataract surgery outcomes study. Br J Ophthalmol 1997;81:102–6.3. Desai P. The National Cataract Surgery Survey: II. Clinical outcomes. Eye 1993;7:489–94.4. Mayer E, Cadman D, Ewings P, et al. A 10 year retrospective survey of cataract surgery and endophthalmitis in a single eye unit:

injectable lenses lower the incidence of endophthalmitis. Br J Ophthalmol 2003;87:867–9.5. Desai P, Minassian DC, Reidy A. National cataract surgery survey 1997–8: a report of the results of the clinical outcomes. Br J

Ophthalmol 1999;83:1336–40.6. Mollan S, Gao A, Lockwood A, et al. Postcataract endophthalmitis: incidence and microbial isolates in a United Kingdom region from

1997 though 2004. J Cataract Refract Surg 2007;33:265–8.7. Anijeet DR, Palimar P, Peckar CO. Intracameral vancomycin following cataract surgery: An eleven-year study. Clin Ophthalmol

2010;4:321–6.8. Kamalarajah S, Ling R, Silvestri G, et al. Surveillance of endophthalmitis following cataract surgery in the UK. Eye 2004;18:580–7.9. Yu-Wai-Man P, Morgan SJ, Hildreth AJ, et al. Efficacy of intracameral and subconjunctival cefuroxime in preventing endophthalmitis

in cataract surgery. J Cataract Refract Surg 2008;34:447–51.10. Haapala TT, Nelimarkka L, Saari JM, et al. Endophthalmitis following cataract surgery in southwest Finland from 1987 to 2000.

Graefes Arch Clin Exp Ophthalmol 2005;243:1010–7.11. Fisch A, Salvanet A, Prazuck T, et al. Epidemiology of infective endophthalmitis in France. The French Collaborative Study Group

on Endophthalmitis. Lancet 1991;338:1373–6.12. Morel C, Gendron G, Tosetti D, et al. Postoperative endophthalmitis: 2000–2002 results in the XV-XX national ophthalmologic

hospital. J Fr Ophtalmol 2005;28:151–6.13. Schmitz S, Dick HB, Krummenauer F, Pfeiffer N. Endophthalmitis in cataract surgery. Results of a German Survey. Ophthalmology

1999;106:1869–77.14. Rummelt V, Bolted HJ, Bialasiewicz AA, Naumann GO. Incidence of postoperative bacterial infections after planned intraocular

Table 1. Endophthalmitis After Cataract Surgery in European Countries, Before the Systematic Use of AntibioticIntracameral Prophylaxis

Country Authors PeriodCataractSurgeries Surgical Technique

PECases

PE Cases per 100Cataracts

Belgium Verbraeken1 1981–1991 3314 ECCE 19 0.573Denmark Norregaard et al2 1985–1987 10 559 ECCE � IOL 19 0.180England Desai3 1990 1445 ECCE predominant 3 0.208England Mayer et al4 1991–2001 18 191 Phaco 62.5% 30 0.165England Desai et al5 1997–1998 15 787 Phaco 77% 26 0.141England Mollan et al6 1997–2004 101 920 Phaco predominant 101 0.099England Anijeet et al7 1998–2000 3904 Phaco predominant 13 0.333England Kamalarajah et al8 1999–2000 152 143 Phaco 92% 213 0.140England Yu-Wai-Man et al9 2001–2003 19 852 Phaco exclusively 34 0.171Finland Haapala et al10 1987–2000 29 350 Phaco 54.27% 47 0.160France Fisch et al11 1988–1989 25 731 ECCE predominant 83 0.323France Morel et al12 2000–2002 13 834 Phaco predominant 36 0.260Germany Schmitz et al13 1996 180 405 Phaco predominant 267 0.148Germany Rummelt V et al14 1984–1988 11 238 ECCE 30 0.267Greece Kalpadaskis et al15 1998–2000 2446 Phaco 56.9% 20 0.818Ireland Khan et al16 1997–2001 8736 Phaco 66% 43 0.492Italy Cedrone et al17 2003 No data No data No data 0.220Netherlands Versteegh et al18 1996–1997 71 028 Phaco 79.6% 108 0.152Norway Sandvig et al19 1996–1998 71 190 Phaco 91% 111 0.156Slovakia Strmen et al20 1993–1995 2374 20 0.840Spain Rubio21 1994–1996 4432 ECCE predominat 18* 0.406Spain Romero et al22 1996–2002 11 696 Phaco (venturi) 100% 76 0.649Spain García-Sáenz et al23 1999–2005 8099 Phaco 90% 39 0.482Spain Garat et al24 2002–2003 5930 Phaco predominant 25 0.422Spain Diez et al25 �2003 No data No data No data 0.500Sweden Montan et al26 1998 54 666 Phaco 92.5% 58 0.100Sweden Montan et al27 1990–1993 22 091 Phaco 33.9% 57 0.258Switzerland Gottrau et al28 1983–1992 6954 8 0.115Total 857 315 1504 0.175

ECCE � extracapsular cataract extraction; IOL � intraocular lens; PE � postoperative endophthalmitis; Phaco � phacoemulsification technique.*18 � data not given in the publication.

interventions. Klin Monbl Augenheilkd 1992;200:178–81.

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15. Kalpadakis P, Tsinopoulos I, Rudolph G, et al. A comparison of endophthalmitis after phacoemulsification or extracapsular cataractextraction in a socio-economically deprived environment: a retrospective analysis of 2446 patients. Eur J Ophthalmol 2002;12:395–400.

16. Khan RI, Kennedy S, Barry P. Incidence of presumed postoperative endophthalmitis in Dublin for a 5-year period (1997–2001). JCataract Refract Surg 2005;31:1575–81.

17. Cedrone C, Ricci F, Regine F, et al. Nationwide incidence of endophthalmitis among the general population and the subjects at riskof endophthalmitis in Italy. Ophthalmic Epidemiol 2008;15:366–71.

18. Versteegh MF, Van Rij G. Incidence of endophthalmitis after cataract surgery in the Netherlands: several surgical techniquescompared. Doc Ophthalmol 2000;100:1–6.

19. Sandvig KU, Dannevig L. Postoperative endophthalmitis: establishment and results of a national registry. J Cataract Refract Surg2003;29:1273–80.

20. Strmen P, Hlavácková K, Ferková S, et al. Endophthalmitis after intraocular interventions. Klin Monbl Augenheilkd 1997;211:245–9.21. Rubio EF. Climatic influence on conjunctival bacteria of patients undergoing cataract surgery. Eye 2004;18:778–84.22. Romero P, Méndez I, Salvat M, et al. Intracameral cefazolin as prophylaxis against endophthalmitis after cataract surgery. J Cataract

Refract Surg 2006;32:438–41.23. García-Sáenz MC, Arias-Puente A, Rodríguez-Caravaca G, Bañuelos JB. Effectiveness of intracameral cefuroxime in preventing

endophthalmitis after cataract surgery. J Cataract Refract Surg 2010;36:203–7.24. Garat M, Moser CL, Martin-Baranera M, et al. Prophylactic intracameral cefazolin after cataract surgery: endophthalmitis risk

reduction and safety results in a 6 years study. J Cataract Refract Surg 2009;35:637–42.25. Díez MR, De la Rosa G, Pascual R, et al. Prophylaxis of postoperative endophthalmitis with intracameral cefuroxime: a five years’

experience. Arch Soc Esp Oftalmol 2009;84:85–9.26. Montan PG, Koranyi G, Setterquist HE, et al. Endophthalmitis after cataract surgery: risk factors relating to technique and events of

the operation and patient history: a retrospective case-control study. Ophthalmology 1998;105:2171–7.27. Montan P, Lundstrom M, Stenevi U, Thorburn W. Endophthalmitis following cataract surgery in Sweden. The 1998 national

prospective survey. Acta Ophthalmol Scand 2002;80:258–61.28. Gottrau P, Leuenberger PM. Postoperative endophthalmitis at the Geneva Ophthalmologic Clinic. Klin Monbl Augenheilkd

1994;204:265–7.

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Figure 2. Endophthalmitis rates per 1000 cataract surgeries in 15 European countries before 2006.

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Figure 3. World average temperatures.

Table 2. Links for United States Incomes and Climate Maps

USA income maps:http://mapsof.net/uploads/static-maps/us_income_map.gifhttp://visualecon.wpengine.netdna-cdn.com/wp-content/uploads/income_map.gifhttp://visualecon.wpengine.netdna-cdn.com/wp-content/uploads/census_2006income.gifUSA climate map:http://printable-maps.blogspot.com/2008/09/climate-maps-united-states-and-canada.htmlUSA temperature maps:http://www.briteresearch.com/images/project_images/us_temp_map.pnghttp://www2m.biglobe.ne.jp/%257EZenTech/English/Climate/USA/index.htmWorld annual temperature maps:

http://en.wikipedia.org/wiki/File:Annual_Average_Temperature_Map.jpg

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