limitations of scheimpflug photography in quantifying glistenings

2
however, the retinal protection by intraocular lenses (IOLs) was independent of age. We will now address 2 additional issues in the letter from Boulton. First, while reviewing the scatter of data after age 60 and after rereading the discussion care- fully, we noted the claimed decrease in Delori et al.’s 2 lipofuscin data after age 70 was ignored. Continuation of the increase of RPE in lipofuscin was assumed in the derivation of age-dependent action spectra. In the discussion of the results, Delori et al. gave several possible explanations for the decrease and large scatter in the data after age 70. These possi- bilities included that individuals with higher lipofus- cin content have developed ARMD and thus were excluded from the study or that individuals with the highest lipofuscin were selectively eliminated from the study because they were less healthy at advanced age and/or may have higher mortality rates. Another possibility is the undercorrection of the fluorescence at ages greater than 70 due to underestimation of lens optical density. Additionally, Delori et al. discussed the possibility of lower fluorescence and thus lower estimates of lipofuscin resulting from the removal of apoptotic RPE cells, leading to a local reduction in lipofuscin fluorescence. Further, we note the absence of any decline in fundus autofluorescence in those 70 years of age or older in the data presented by von Ru ¨ ckmann et al. 3 With such a list of possibilities and uncertainties in addition to the tremendous scatter of lipofuscin fluorescence data after age 60, the continu- ing increase in lipofuscin accumulation is a safe as- sumption for surviving RPE. Second, Boulton states that our study has a major limitation because we modeled our calculations on A2E only. Our results do indicate that the 420 to 480 nm wavelength range, in which significant absor- bance of the A2E component occurs, is the most discrim- inative range for protection provided by the IOLs. However, we also provided calculations for relative ret- inal phototoxicity and protection by the selected IOLs for 2 other wavelength bands, 300 to 700 nm and 400 to 550 nm. We agree that besides A2E there may be other photoreactive substances in lipofuscin and look forward to progress in research that may refine the mechanism of blue light’s role in lipofuscin accumulation-mediated retinal phototoxicity. We also agree that the potential for lipofuscin-related phototoxicity is greatest in areas of focal hyperpigmentation, which are closely associ- ated with the progression of geographic atrophy. Our paper focused on the comparative protection from IOLs only; as in the paper, we continue to refrain from the discussion about the myth or realty of the role of retinal lipofuscin–mediated phototoxicity as a risk factor for ARMD. But we note that the latest EUREYE epidemiologic study 4 shows a significant association between blue-light exposure and neovascular ARMD in individuals with the lowest level of antioxidants in their blood. This association may be linked to the finding of the blue light–induced in vitro generation of oxygen-reactive species for RPE lipofuscin and may thereby support the hypothesis for potential reti- nal photodamage and contribution to the develop- ment of ARMD, as postulated in Ro ´ _ zanowska et al.’s paper.dDennis Carson, PhD, Tom H. Margrain, PhD, Anil Patel, PhD REFERENCES 1. Ro ´ _ zanowska M, Jarvis-Evans J, Korytowski W, Boulton ME, Burke JM, Sarna T. Blue light-induced reactivity of retinal age pig- ment; in vitro generation of oxygen-reactive species. J Biol Chem 1995; 270:18825–18830. Available at: http://www.jbc.org/cgi/ reprint/270/32/18825. Accessed April 6, 2009 2. Delori FC, Goger DG, Dorey CK. Age-related accumulation and spatial distribution of lipofuscin in RPE of normal subjects. Invest Ophthalmol Vis Sci 2001; 42:1855–1866. Available at: http:// www.iovs.org/cgi/reprint/42/8/1855. Accessed April 13, 2009 3. von Ru ¨ckmann A, Fitze FW, Bird AC. Fundus autofluorescence in age-related macular disease imaged with a laser scanning ophthalmoscope. Invest Ophthalmol Vis Sci 1997; 38:478–486. Available at: http://www.iovs.org/cgi/reprint/38/2/478.pdf. Accessed April 13, 2009 4. Fletcher AE, Bentham GC, Agnew M, Young IS, Augood C, Chakravarthy U. de Jong PTVM, Rahu M, Seland J, Soubrane G, Tomazzoli L, Topouzis F, Vingerling JR, Vioque J. Sunlight exposure, antioxidants, and age-related macular degeneration. Arch Ophthalmol 2008; 126:1396–1403 Limitations of Scheimpflug photography in quantifying glistenings Behndig and Mo ¨ nestam 1 have described Scheimp- flug photography for quantifying glistenings in intra- ocular lenses (IOLs). We believe the technique is unsuitable for this purpose. The authors measured the intensity of scattered light through the IOL. There is no demonstration of the ability to distinguish between light scatter due to glistenings and light scat- ter due to other more likely variables, such as the aque- ous–IOL interface or biological materials on the IOL surface. 2 The observed scatter is primarily at the IOL surfaces, whereas glistenings are more prevalent within the IOL. Glistenings are small (3 to 10 mm), 3,4 irregularly dis- tributed microvacuoles within the IOL. As they are irregularly placed, it is not evident how the microva- cuoles would generate the systematic intensity distri- butions depicted in the graphs. We believe analysis of glistenings requires a more discrete analytical approach. The reported correlation coefficients for the given intensity profiles (interpreted as glistenings) and postoperative time were higher for Scheimpflug 1480 LETTERS J CATARACT REFRACT SURG - VOL 35, AUGUST 2009

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Page 1: Limitations of Scheimpflug photography in quantifying glistenings

however, the retinal protection by intraocular lenses(IOLs) was independent of age.

We will now address 2 additional issues in the letterfrom Boulton. First, while reviewing the scatter of dataafter age 60 and after rereading the discussion care-fully, we noted the claimed decrease in Deloriet al.’s2 lipofuscin data after age 70 was ignored.Continuation of the increase of RPE in lipofuscin wasassumed in the derivation of age-dependent actionspectra. In the discussion of the results, Delori et al.gave several possible explanations for the decreaseand large scatter in the data after age 70. These possi-bilities included that individuals with higher lipofus-cin content have developed ARMD and thus wereexcluded from the study or that individuals with thehighest lipofuscin were selectively eliminated fromthe study because they were less healthy at advancedage and/or may have higher mortality rates. Anotherpossibility is the undercorrection of the fluorescence atages greater than 70 due to underestimation of lensoptical density. Additionally, Delori et al. discussedthe possibility of lower fluorescence and thus lowerestimates of lipofuscin resulting from the removal ofapoptotic RPE cells, leading to a local reduction inlipofuscin fluorescence. Further, we note the absenceof any decline in fundus autofluorescence in those70 years of age or older in the data presented by vonRuckmann et al.3 With such a list of possibilities anduncertainties in addition to the tremendous scatter oflipofuscin fluorescence data after age 60, the continu-ing increase in lipofuscin accumulation is a safe as-sumption for surviving RPE.

Second, Boulton states that our study has a majorlimitation because we modeled our calculations onA2E only. Our results do indicate that the 420 to480 nm wavelength range, in which significant absor-bance of theA2E component occurs, is themostdiscrim-inative range for protection provided by the IOLs.However, we also provided calculations for relative ret-inal phototoxicity and protection by the selected IOLsfor 2 other wavelength bands, 300 to 700 nm and 400to550nm.Weagree that besidesA2E theremaybeotherphotoreactive substances in lipofuscinand look forwardtoprogress in research thatmay refine themechanismofblue light’s role in lipofuscin accumulation-mediatedretinal phototoxicity. We also agree that the potentialfor lipofuscin-related phototoxicity is greatest in areasof focal hyperpigmentation, which are closely associ-ated with the progression of geographic atrophy.

Our paper focused on the comparative protectionfrom IOLs only; as in the paper, we continue to refrainfrom the discussion about themyth or realty of the roleof retinal lipofuscin–mediated phototoxicity as a riskfactor for ARMD. But we note that the latest EUREYEepidemiologic study4 shows a significant association

between blue-light exposure and neovascular ARMDin individuals with the lowest level of antioxidantsin their blood. This association may be linked to thefinding of the blue light–induced in vitro generationof oxygen-reactive species for RPE lipofuscin andmay thereby support the hypothesis for potential reti-nal photodamage and contribution to the develop-ment of ARMD, as postulated in Ro _zanowska et al.’spaper.dDennis Carson, PhD, Tom H. Margrain, PhD,Anil Patel, PhD

REFERENCES1. Ro _zanowska M, Jarvis-Evans J, Korytowski W, Boulton ME,

Burke JM, Sarna T. Blue light-induced reactivity of retinal age pig-

ment; in vitro generation of oxygen-reactive species. J Biol Chem

1995; 270:18825–18830. Available at: http://www.jbc.org/cgi/

reprint/270/32/18825. Accessed April 6, 2009

2. Delori FC, Goger DG, Dorey CK. Age-related accumulation and

spatial distribution of lipofuscin in RPE of normal subjects. Invest

Ophthalmol Vis Sci 2001; 42:1855–1866. Available at: http://

www.iovs.org/cgi/reprint/42/8/1855. Accessed April 13, 2009

3. von Ruckmann A, Fitze FW, Bird AC. Fundus autofluorescence

in age-related macular disease imaged with a laser scanning

ophthalmoscope. Invest Ophthalmol Vis Sci 1997; 38:478–486.

Availableat: http://www.iovs.org/cgi/reprint/38/2/478.pdf.Accessed

April 13, 2009

4. Fletcher AE, Bentham GC, Agnew M, Young IS, Augood C,

Chakravarthy U. de Jong PTVM, Rahu M, Seland J, Soubrane

G, Tomazzoli L, Topouzis F, Vingerling JR, Vioque J. Sunlight

exposure, antioxidants, and age-related macular degeneration.

Arch Ophthalmol 2008; 126:1396–1403

1480 LETTERS

J CATARACT REFRACT SURG

Limitations of Scheimpflug photographyin quantifying glistenings

Behndig and Monestam1 have described Scheimp-flug photography for quantifying glistenings in intra-ocular lenses (IOLs). We believe the technique isunsuitable for this purpose. The authors measuredthe intensity of scattered light through the IOL. Thereis no demonstration of the ability to distinguishbetween light scatter due to glistenings and light scat-ter due to othermore likely variables, such as the aque-ous–IOL interface or biological materials on the IOLsurface.2 The observed scatter is primarily at the IOLsurfaces, whereas glistenings are more prevalentwithin the IOL.

Glistenings are small (3 to 10 mm),3,4 irregularly dis-tributed microvacuoles within the IOL. As they areirregularly placed, it is not evident how the microva-cuoles would generate the systematic intensity distri-butions depicted in the graphs. We believe analysisof glistenings requires a more discrete analyticalapproach.

The reported correlation coefficients for the givenintensity profiles (interpreted as glistenings) andpostoperative time were higher for Scheimpflug

- VOL 35, AUGUST 2009

Page 2: Limitations of Scheimpflug photography in quantifying glistenings

imaging and vice versa. For example, in poly(methylmethacrylate) IOLs without clinically detectable glis-tenings, light scattering is also absent in the Scheimp-flug images. (4) The IOL surfaces are distinguishablewith the high-resolution Scheimpflug system we use,and the light scattering does arise from within theIOL material, albeit more intense near the IOL sur-faces. Furthermore, as indicated, we used only thetotal light scattering within the central 1.5 mm zoneof the IOL in our calculations and did not considerthe axial location of the glistenings.

In summary, ‘‘posterior capsule opacification ordebris on a lens’’ can be ruled out as a source of thelight scattering observed in our material, both clini-cally and with Scheimpflug imaging. Based on ourcurrent expanded analysis using the same methods,we are confident (as many before us have been1–6)that Scheimpflug photography is a reproducible andaccurate way to quantify light scattering in the eye’santerior segment, including IOLs.dAnders Behndig,MD, PhD, Eva Monestam, MD, PhD

REFERENCES1. Klos KM, Richter R, Schnaudigel O-E, Ohrloff C. Image analysis

of implanted rigid and foldable intraocular lenses in human eyes

using Scheimpflug photography. Ophthalmic Res 1999;

31:130–133

2. Ayaki M, Nishihara H, Yaguchi S, Koide R. Surfactant induced

glistenings: surface active ingredients in ophthalmic solutions

may enhance water entry into the voids of implanted acrylic intra-

ocular lenses. J Long Term Eff Med Implants 2006; 16:451–457

3. Palmquist B-M, Fagerholm P, Landau I. Selenium-induced cata-

ract – a correlation of dry mass content and light scattering. Exp

Eye Res 1986; 42:35–42

4. Busin M, Spitznas M, Laser H, Leyendecker M, Hockwin O. In

vivo evaluation of epikeratophakia lenses by means of Scheimp-

flug photography. Refract Corneal Surg 1989; 5:155–160

5. Bours J, Ahrend MHJ, Wegener A, Hockwin O. Water-insoluble

high-molecular-weight and alpha-crystallins as the source of the

Scheimpflug light scattering pattern in the rat lens. Ophthalmic

Res 1990; 22(suppl 1):90–94

6. Sasaki K, Fujisawa K, Sakamoto Y. Quantitative evaluation of

nuclear cataract using image analysis. Ophthalmic Res 1992;

24(suppl 1):26–31

1481LETTERS

photography than for subjective grading. Rather thanindicating that Scheimpflug imaging is reliable, as theauthors conclude, it more likely indicates that the im-aging is unrelated to glistenings and perhaps more re-lated to posterior capsule opacification or debris on anIOL, both likely to increase over time.

Scheimpflug photography’s off-axis illuminationcan produce significant light scattering even in a clearcornea. This is evident in a cross-sectional photo fromRosales et al.5 in which scatter from a young cornea ishigher than from the model eye cornea and lens ora human crystalline lens. Scatter from the Scheimpflugimage should not be interpreted as clinicallyconsequential.

The limited resolution of the light-scatter intensity,a bias toward IOL borders, and a lack of correlationwith clinical observation suggest Scheimpflugimaging is not suitable for characterization of IOLglistenings.

Richard J. Mackool, MDAstoria, New York, USA

Joseph Colin, MDBordeaux, France

REFERENCES1. Behndig A, Monestam E. Quantifications of glistenings in intraoc-

ular lenses using Scheimpflug photography. J Cataract Refract

Surg 2009; 35:14–17

2. Yaguchi S, Nishihara H, Kambhiranond W, Stanley D, Apple DJ.

Light scatter on the surface of AcrySof� intraocular lenses: part II.

Analysis of lenses following hydrolytic stability testing. Ophthal-

mic Surg Lasers Imaging 2008; 39:214–216

3. Omar O, Pirayesh A, Mamalis N, Olson RJ. In vitro analysis of

AcrySof intraocular lens glistenings in AcryPak and Wagon

Wheel packaging. J Cataract Refract Surg 1998; 24:107–113

4. Miyata A, Uchida N, Nakajima K, Yaguchi S. [Clinical and

experimental observation of glistening in acrylic intraocular

lenses]. [Japanese] Nippon Ganka Gakkai Zasshi 2000;

104:349–353

5. Rosales P, Marcos S. Pentacam Scheimpflug quantitative imag-

ing of the crystalline lens and intraocular lens. In press, J Refract

Surg 2009

REPLY: We thank Mackool and Colin for sharingtheir view of Scheimpflug photography and IOL glis-tenings. We think a few things need to be emphasizedor clarified: (1) Scheimpflug photography has beendescribed for quantification of IOL glistenings, origi-nally by Klos et al. in 19991 and later by Ayaki et al.,2

as indicated in our report. (2) Cases with posterior cap-sule opacification or deposits on the IOL surface werenot included in our analysis. (3) We are currently ana-lyzing a larger cohort and in our expanded analyses,IOL glistenings are seen clinically in the slitlampwhen light scattering is observed with Scheimpflug

Diurnal fluctuation of IOL power calculationin glaucomatous eyes

In their Swedish National Cataract Register study,Kugelberg and Lundstrom1 stated that glaucomawas significantly related to a large deviation fromthe target postoperative refraction in eyes scheduledfor cataract surgery. We offer an explanation for thisfinding.

A recent study demonstrated that intraocular pres-sure (IOP), ocular pulse amplitude, and choroidal thick-ness significantly increase during the water-drinking

J CATARACT REFRACT SURG - VOL 35, AUGUST 2009