Retinal Function in Diabetic Macular Edema after Focal Laser Photocoagulation

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Retinal Function in Diabetic Macular Edema after Focal Laser Photocoagulation Vivienne C. Greenstein, 1 Haifan Chen, 1 Donald C. Hood, 2 Karen Holopigian, 1 William Seiple, 1 and Ronald E. Carr 1 PURPOSE. To assess the effects of focal photocoagulation on retinal function in the macular and perimacular areas in patients with diabetes who have clinically significant macular edema. METHODS. Eleven patients were assessed after focal laser treatment. Multifocal electroretinogram (ERG) and full-field ERG techniques were used to evaluate the effects of treatment on macular, paramacular, and peripheral retinal function. A modified visual field technique was used to obtain local threshold fields. The posttreatment results were compared with pretreatment results. Changes in local ERG response amplitudes and implicit times were calculated for each patient and presented as difference fields. The changes in local ERG responses were compared with the changes in local field sensitivity. RESULTS. After treatment, the results of the psychophysical tests suggested little or no change in visual function, but changes in retinal function were observed with the multifocal ERG technique. Local ERG responses showed increases in implicit time and decreases in amplitude, compared with pretreatment values. Timing was affected more than amplitude. CONCLUSIONS. The results suggest that focal treatment produces changes in retinal function, and these changes are not restricted to the treated macular area. (Invest Ophthalmol Vis Sci. 2000;41: 3655–3664) T he beneficial effects of focal photocoagulation for clin- ically significant diabetic macular edema (CSME) have been demonstrated in a series of clinical trials. 1,2 Visual acuity is stabilized, and the risk of loss in visual acuity is substantially reduced. 1 However, visual acuity measurements provide information about only one aspect of the impaired visual function that accompanies CSME. As shown in an ac- companying article in this issue, 3 visual function can be af- fected in the fovea, the macula, and in surrounding retinal areas. It is therefore important to be able to monitor any change that may occur in these regions after focal photocoag- ulation treatment. The few studies that have investigated the effects of treatment on extrafoveal function have used either visual field or pattern electroretinogram (PERG) techniques. 4–6 Focal photocoagulation was reported to decrease visual field sensitivities in the central 10°, whereas sensitivities in areas outside the treated area remained stable. 5,6 A study using the PERG technique showed that amplitudes were markedly de- creased after focal treatment. 4 The effects of focal treatment on local ERG activity remain to be determined. It is only in the past few years that techniques have become available for mea- suring local ERG activity simultaneously at multiple sites. In this study, we used visual field and multifocal ERG techniques to measure changes in local retinal function that may occur in the macular and perimacular area after focal photocoagulation. METHODS Subjects Eleven patients with clinically significant macular edema who participated in the first part of the study were treated with focal argon green laser photocoagulation. The term focal refers to two types of photocoagulation treatment, localized and grid. The age range of the patients was 33 to 67 years (mean, 56.5 6 9 years). Slit lamp biomicroscopy, color fundus photographs, and fluorescein angiography were used to determine the level of retinopathy and degree of macular edema and to identify treatable areas. The pretreatment clinical characteristics of the patients are summarized in Table 1. For the nine patients with macular edema classified as intermediate, treatment consisted of argon green laser spots of 50 to 100 mm applied to leaking microaneurysms and a modified grid to areas of diffuse edema. The endpoint was defined as a slight graying at the microan- eurysm site or in the grid pattern. The two patients with diffuse leakage were treated with argon green laser in a grid pattern. Treatment consisted of 100 to 200 light burns of 100 to 200 mm spot size lasting 0.1 seconds. A space of one burn width was left between each grid lesion. To minimize the effects of reactive edema, patients were tested between 8 and 12 weeks after treatment. In addition to ERG and psychophysical testing, follow-up fluorescein angiography, photography, and biomi- From the 1 Department of Ophthalmology, New York University School of Medicine, and the 2 Department of Psychology, Columbia University, New York, New York. Supported by National Eye Institute grant R01-EY-02115, an unre- stricted grant to the Department of Ophthalmology from Research to Prevent Blindness, and grants from the Helen Hoffritz Foundation and the Allene Reuss Memorial Trust. Submitted for publication March 17, 2000; accepted April 13, 2000. Commercial relationships policy: N. Corresponding author: Vivienne C. Greenstein, Department of Ophthalmology, NYU Medical Center, 550 First Avenue, New York, NY 10016. [email protected] Investigative Ophthalmology & Visual Science, October 2000, Vol. 41, No. 11 Copyright © Association for Research in Vision and Ophthalmology 3655

Transcript of Retinal Function in Diabetic Macular Edema after Focal Laser Photocoagulation

Retinal Function in Diabetic Macular Edema after FocalLaser Photocoagulation

Vivienne C. Greenstein,1 Haifan Chen,1 Donald C. Hood,2 Karen Holopigian,1

William Seiple,1 and Ronald E. Carr1

PURPOSE. To assess the effects of focal photocoagulation on retinal function in the macular andperimacular areas in patients with diabetes who have clinically significant macular edema.

METHODS. Eleven patients were assessed after focal laser treatment. Multifocal electroretinogram(ERG) and full-field ERG techniques were used to evaluate the effects of treatment on macular,paramacular, and peripheral retinal function. A modified visual field technique was used to obtainlocal threshold fields. The posttreatment results were compared with pretreatment results.Changes in local ERG response amplitudes and implicit times were calculated for each patient andpresented as difference fields. The changes in local ERG responses were compared with thechanges in local field sensitivity.

RESULTS. After treatment, the results of the psychophysical tests suggested little or no change invisual function, but changes in retinal function were observed with the multifocal ERG technique.Local ERG responses showed increases in implicit time and decreases in amplitude, compared withpretreatment values. Timing was affected more than amplitude.

CONCLUSIONS. The results suggest that focal treatment produces changes in retinal function, andthese changes are not restricted to the treated macular area. (Invest Ophthalmol Vis Sci. 2000;41:3655–3664)

The beneficial effects of focal photocoagulation for clin-ically significant diabetic macular edema (CSME) havebeen demonstrated in a series of clinical trials.1,2 Visual

acuity is stabilized, and the risk of loss in visual acuity issubstantially reduced.1 However, visual acuity measurementsprovide information about only one aspect of the impairedvisual function that accompanies CSME. As shown in an ac-companying article in this issue,3 visual function can be af-fected in the fovea, the macula, and in surrounding retinalareas. It is therefore important to be able to monitor anychange that may occur in these regions after focal photocoag-ulation treatment. The few studies that have investigated theeffects of treatment on extrafoveal function have used eithervisual field or pattern electroretinogram (PERG) techniques.4–6

Focal photocoagulation was reported to decrease visual fieldsensitivities in the central 10°, whereas sensitivities in areasoutside the treated area remained stable.5,6 A study using thePERG technique showed that amplitudes were markedly de-creased after focal treatment.4 The effects of focal treatment onlocal ERG activity remain to be determined. It is only in the

past few years that techniques have become available for mea-suring local ERG activity simultaneously at multiple sites. Inthis study, we used visual field and multifocal ERG techniquesto measure changes in local retinal function that may occur inthe macular and perimacular area after focal photocoagulation.

METHODS

Subjects

Eleven patients with clinically significant macular edema whoparticipated in the first part of the study were treated withfocal argon green laser photocoagulation. The term focal refersto two types of photocoagulation treatment, localized and grid.The age range of the patients was 33 to 67 years (mean, 56.5 69 years). Slit lamp biomicroscopy, color fundus photographs,and fluorescein angiography were used to determine the levelof retinopathy and degree of macular edema and to identifytreatable areas. The pretreatment clinical characteristics of thepatients are summarized in Table 1. For the nine patients withmacular edema classified as intermediate, treatment consistedof argon green laser spots of 50 to 100 mm applied to leakingmicroaneurysms and a modified grid to areas of diffuse edema.The endpoint was defined as a slight graying at the microan-eurysm site or in the grid pattern. The two patients with diffuseleakage were treated with argon green laser in a grid pattern.Treatment consisted of 100 to 200 light burns of 100 to 200mm spot size lasting 0.1 seconds. A space of one burn widthwas left between each grid lesion. To minimize the effects ofreactive edema, patients were tested between 8 and 12 weeksafter treatment. In addition to ERG and psychophysical testing,follow-up fluorescein angiography, photography, and biomi-

From the 1Department of Ophthalmology, New York UniversitySchool of Medicine, and the 2Department of Psychology, ColumbiaUniversity, New York, New York.

Supported by National Eye Institute grant R01-EY-02115, an unre-stricted grant to the Department of Ophthalmology from Research toPrevent Blindness, and grants from the Helen Hoffritz Foundation andthe Allene Reuss Memorial Trust.

Submitted for publication March 17, 2000; accepted April 13,2000.

Commercial relationships policy: N.Corresponding author: Vivienne C. Greenstein, Department of

Ophthalmology, NYU Medical Center, 550 First Avenue, New York,NY 10016. [email protected]

Investigative Ophthalmology & Visual Science, October 2000, Vol. 41, No. 11Copyright © Association for Research in Vision and Ophthalmology 3655

croscopy, were performed in all cases. In eight patients theright eye was treated and tested, and in the remaining threepatients, the left eye was treated and tested. In Figures 3 and 4the multifocal records and visual field for the left eye of one ofthese patients are reversed to provide easier comparisonsamong patients.

Nine control subjects ranging in age from 40 to 62 years(mean, 51.6 6 8 years) with no known abnormalities of thevisual system also participated in the study. All had normalfull-field ERGs and normal findings in ophthalmic examina-tions. Informed consent was obtained from all subjects beforetheir participation. Procedures followed the tenets of the Dec-laration of Helsinki, and the protocol was approved by thecommittee of the Institutional Board of Research Associatesof New York University School of Medicine and BellevueHospital.

Multifocal ERG Technique

Multifocal ERGs were recorded using the Veris (EDI, San Ma-teo, CA) technique (for details see Sutter and Tran7 and Sut-ter8). The visual stimulus consisted of 103 hexagonal areasscaled with eccentricity. Each hexagonal area was modulatedfrom black to white independently according to a binary m-sequence (Lmax 5 400 candelas [cd]/m2 and Lmin 5 9 cd/m2.For details see Hood et al.,9 and Greenstein et al.3

As in the first study, to optimize the identification oflocalized changes that may occur after treatment to the macu-lar area, patients (P)1 through P5 were tested with the monitorpositioned at a viewing distance of 64 cm. At this viewingdistance the 103 hexagons fell within a field of approximately28° by 22°. The m-sequence stimulation rate was slowed toallow for the assessment of macular oscillatory potentials(OPs)10,11 by inserting four frames between consecutive stim-ulus frames. For patients P6 through P11, the monitor waspositioned at a viewing distance of 32 cm, the hexagons fellwithin a larger field of approximately 47° (width) by39°(height), and the m-sequence stimulation rate was the sameas the monitor’s frame rate (see Greenstein et al.3 for details).

Recording Technique and Analysisof Multifocal Responses

The recording technique was the same as that described inGreenstein et al.3

The amplitudes and implicit times of the individual mul-tifocal responses were calculated using a computer softwareprogram (MATLAB; The MathWorks, Natick, MA). For detailssee Greenstein et al.3 and Hood and Li.12

Full-field ERG

As in the first study, full-field cone ERGs were measured usinga photostimulator (Grass Instruments, Quincy, MA) in a Ganz-feld. After 5 minutes of light adaptation to a white Ganzfeld of40 cd/m2, full-field cone ERGs were obtained to 30-Hz flicker.The signal was amplified (1 K; preamplifier model P511J;Grass) and filtered (1–10,000 Hz).

Visual Fields

To compare multifocal data with visual field data, thresholdswere measured on a Humphrey perimeter (Humphrey, SanLeandro, CA) at either 103 locations that corresponded to thecenters of the 103 hexagonal areas in the multifocal displayviewed at 32 cm or 58 locations that corresponded to thecenters of 58 of the 103 hexagonal areas viewed at 64 cm. Thebackground luminance was 10 cd/m2.

RESULTS

Clinical Findings

The relevant posttreatment clinical findings are summarized inTable 1. Edema appeared to be resolved in four of the ninepatients classified as having intermediate CSME. Four had re-sidual edema, and one showed no change. For the two patientswith diffuse edema, one showed no change, and the other hadresidual edema. Posttreatment visual acuities ranged from 20/200 to 20/25. Only two of the patients, P2 and P9, showed asignificant improvement in visual acuity (an improvement of

TABLE 1. Clinical Characteristics of Patients

Patient Age Level DR*Classification

of CSME†

Visual Acuity

Posttreatment CSMEEvaluationPretreatment Posttreatment

1 60 4 I 20/200 (.10) 20/200 (.10) Unchanged2 53 3 I 20/80 (.25) 20/50 (.40) Residual3 33 6 D 20/50 (.40) 20/50 (.40) Unchanged4 52 3 I 20/50 (.40) 20/40 (.50) Resolved5 62 4 D 20/40 (.50) 20/30 (.67) Residual6 59 3 I 20/40 (.50) 20/30 (.67) Residual7 54 3 I 20/30 (.67) 20/25 (.80) Resolved8 67 3 I 20/40 (.50) 20/40 (.50) Residual9 60 3 I 20/100 (.20) 20/70 (.28) Residual

10 65 3 I 20/30 (.67) 20/30 (.67) Resolved11 57 3 I 20/30 (.67) 20/40 (.50) Resolved

Values in parentheses represent visual acuity expressed as a decimal.* Classification of level of diabetic retinopathy (DR): Level 3: microaneurysms with one or more other nonproliferative lesions present of mild

to moderate degree; level 4: microaneurysms with one or more other nonproliferative lesions present of severe degree; level 5: severe overallnonproliferative retinopathy; level 6: proliferative retinopathy without diabetic retinopathy high-risk characteristics.

† Classification of CSME (based on fluorescein angiograms): I, intermediate with approximately equal leakage from microaneurysms and dilatedcapillaries; D, diffuse with leakage mainly from dilated capillaries.

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more than one line on a Snellen acuity chart). The results forthe other patients were consistent with a stabilization of acuity(either no change or an increase or decrease equivalent to oneline on a Snellen acuity chart). In summary, treatment had littleeffect on visual acuity.

Full-field ERG

After treatment, none of the patients showed a significantchange in amplitude for 30-Hz full-field flicker. Before treat-ment, 7 of the 11 patients had significantly delayed implicittimes. Of these seven patients, P1 and P6 showed additionaldelays in implicit time of approximately 3 msec (Table 2).Implicit times for the other four patients, although slightlyincreased after treatment (0.4–2.5msec), remained within thenormal range.

Multifocal ERGs

Examples of multifocal ERG responses obtained from two ofthe patients, P1 (slow sequence and smaller stimulus field) andP9 (fast sequence and larger stimulus field), before and afterlaser treatment are shown in Figure 1. For both patients,amplitudes were decreased and implicit times were increasedafter treatment. This was easier to see when amplitude andimplicit times for the individual responses were measured. Toassess the effects of treatment, the amplitudes and implicittimes of the individual responses for all subjects were mea-sured as previously described.3,12 The values obtained from thecontrol subjects were used to obtain a mean control implicittime and mean control peak-to-trough amplitude for each ofthe 103 test locations. Pre- and posttreatment amplitude lossand implicit time delay were calculated for each of the pa-tient’s responses (see Greenstein et al.3 for details of calculat-

FIGURE 1. Multifocal records fortwo patients before and after lasertreatment. Left: Records for P1 wereobtained using the slowed m-se-quence and a stimulus display sub-tending 28° by 22°; right: records forP9 were obtained using the fast m-sequence and stimulus display sub-tending 47° by 39°.

TABLE 2. Amplitudes and Implicit Times

Patient

Pretreatment Posttreatment

30-HzAmplitude*

30-HzImplicitTime†

30-HzAmplitude*

30-HzImplicitTime†

1 125 32.2‡ 117 35.2‡2 92.2 32‡ 66.1 31.33 71.4 35.6‡ 96.3 34.7‡4 119 32.2‡ 113 32.7‡5 139 32.7‡ 137.1 31.26 84.2 33.2‡ 76.7 36.6‡7 134.5 30 141.7 31.38 77.2 28.3 93.8 30.89 77 36.6‡ 62 34.7‡

10 91 26 99 2711 138.1 31.3 111 31.7

* Mean normal amplitude: 126 6 45 mV (SD).† Mean normal implicit time: 28 6 2 msec (SD).‡ Significant delay in implicit time compared with control sub-

jects.

IOVS, October 2000, Vol. 41, No. 11 Effects of Focal Laser Treatment on Retinal Function 3657

ing amplitude loss and implicit time delay). Figures 2 and 3show the multifocal ERG delay and amplitude loss fields ob-tained pre- and posttreatment from P1 and P3. The numbers inthe delay fields (Figs. 2, 3, left) are the delays rounded to thenearest milliseconds. Delays within 1 SD of the mean value forthat location are represented by white hexagons, delays be-tween 1 and 2 SDs of the mean value by light gray hexagons,and delays greater than 2 SDs of the mean value by dark grayhexagons. Black hexagons without numbers represent poortemplate fits (see Methods in Greenstein et al.3). For the am-plitude loss fields (Figs. 2, 3, right) the numbers represent thedifference in microvolts at each location between the patient’strough-to-peak amplitude and the mean normal amplitude forthat location. Decreases in amplitude within 1 SD of the meanvalue are represented by white hexagons; decreases between 1and 2 SDs of the mean are represented by light gray hexagons;and decreases greater than 2 SDs are represented by dark grayhexagons.

As can be seen in Figures 2 and 3, the responses for P1 andP3 were delayed and decreased in amplitude, both before andafter laser treatment. For both patients, timing was more af-fected than amplitude, and timing abnormalities involved alarger area of the field. After treatment, the local ERG re-

sponses for P1 showed additional delays in timing, particularlyin the superior field (inferior retinal region), and additionaldecreases in response amplitude. In contrast, for P3, responsedelays had decreased and amplitudes had increased after treat-ment. To obtain a quantitative measure of these changes thedifferences between the pre- and posttreatment implicit timesand amplitudes were calculated for each patient. Figure 4shows the data for P1 and P3 presented in the form of differ-ence fields. The numbers in the delay difference fields (Fig. 4,left) represent the differences between the patient’s post- andprelaser implicit times in milliseconds. The change in ampli-tude for each of the patients’ responses was calculated in asimilar way. The postlaser peak-to-trough amplitude for eachresponse was compared with the prelaser peak-to-trough am-plitude at the same location. The numbers in the amplitudeloss fields (Fig. 4, right) represent the difference in microvoltsbetween the patient’s post- and prelaser trough-to-peak ampli-tudes.

To provide some indication of the magnitude of thechanges, the results were compared with changes in implicittimes and amplitudes obtained from seven control subjectswho were retested after 1 year. The light gray hexagons rep-resent increases in implicit time or decreases in amplitude

FIGURE 2. Pretreatment and posttreatment ERG delay fields (left) and amplitude loss fields (right) for P1.

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between 2 and 3 SDs of the values obtained for the sevencontrol subjects. Dark gray hexagons represent changes thatexceeded 3 SDs of the values obtained for control subjects, andblack hexagons represent poor template fits—that is, fits ex-ceeding the statfit criterion of 0.75 described in the Methodssection. White hexagons represent no change, or decreases intiming and increases in amplitude. Decreases in timing andincreases in amplitude that exceeded 2 SDs (i.e., a significantimprovement) are represented by numbers in bold underlinedtext. White hexagons also represent relative increases in timingor decreases in amplitude whose values are within 2 SDs of thevalues obtained for the control subjects. The difference fieldsfor P1 indicate that retinal function continued to deteriorateafter treatment (Fig. 4, top). Timing was more affected thanamplitude; there were locations that showed additional in-creases in implicit time but no change in amplitude. Thedifference fields for P2, P4, and P5 (not shown) also indicateddeterioration after treatment, in that additional increases inimplicit time were found. The difference fields for P3 (Fig. 4,bottom panels) in contrast, were consistent with an improve-ment in retinal function. For this patient, there were increasesin response amplitude and decreases in implicit time, particu-larly in the superior field.

The changes in implicit time and amplitude for P1 throughP5 after laser treatment are summarized in Figure 5A. The pointin the center of each box represents the median change inimplicit time or amplitude for the 103 responses. The box plotsindicate quartiles (25th and 75th percentiles of each distribu-tion). The whiskers indicate the range of values. For the con-trol subjects (hatched box) who were retested after 1 year,there were minimal changes in median implicit time and am-plitude but the changes in amplitude were slightly more vari-able. For the patients, median implicit times were increased forP1, P2, and P4 and decreased for P3. The majority of the datapoints for these patients fell outside the range of values ob-tained for the control group. The increases in median implicittimes for P1 and P4 were accompanied by decreases in medianamplitude and for P3 the decrease in implicit time was accom-panied by an increase in amplitude. These results were ob-tained from the patients 2 months after treatment. We wereable to obtain additional multifocal ERG data from P1 and P5 5months after laser treatment. The changes in implicit times andamplitudes after laser treatment at 2 and at 5 months aresummarized in Figure 5B. At 5 months, both patients showedadditional slight increases in implicit time and little or nochange in amplitude.

FIGURE 3. Pretreatment and posttreatment ERG delay fields (left) and amplitude loss fields (right) for P3.

IOVS, October 2000, Vol. 41, No. 11 Effects of Focal Laser Treatment on Retinal Function 3659

The stimulus conditions for P1 through P5 were chosennot only to optimize the resolution of localized changes thatmay occur both before and after focal laser treatment of CSMEbut also to allow for assessment of macular OPs. Before treat-ment, the OPs and a late component at approximately 50 to 55msec appeared to be absent or nonrecordable in all five pa-tients. After treatment, there appeared to be no change. Similarsmooth waveforms were observed, and the OPs and a latecomponent were either absent or nonrecordable.

The differences between the pre- and posttreatment im-plicit times and amplitudes were also calculated for the pa-tients, P6 through P11, who were tested with the fastm-sequence. For four of the patients P6, P7, P9, and P10, themultifocal ERG responses obtained with the larger stimulus

field and more conventional stimulus sequence rate alsoshowed increases in implicit time after treatment. The differ-ence fields for two of these patients P6 and P9 are shown inFigure 6. For P6 in the central part of the field some of theresponses showed significant decreases in implicit time andincreases in amplitude (see numbers in bold text).

The changes in implicit time and amplitude for the macularand perimacular areas of P6 through P11 are summarized inFigure 7. For the macular area, the changes in implicit times andamplitudes for the central 41 hexagons were calculated (a stim-ulus area equivalent to that used for P1 through P5). The controlsubjects showed minimal changes in median implicit time andresponse amplitude when retested after a year. For the patients,treatment had the effect of increasing implicit times for P7, P9,

FIGURE 4. Difference fields for P1 (top) and P3 (bottom). The numbers in the delay difference fields (left) represent the differences betweenthe patient’s post- and prelaser implicit times in milliseconds. The numbers in the amplitude difference fields (right) represent the differencein microvolts between the patient’s post- and prelaser trough-to-peak amplitude. The light gray hexagons represent increases in implicit timeor decreases in amplitude between 2 and 3 SDs of the values for control subjects; dark gray hexagons, changes that exceed 3 SDs of thevalues obtained for control subjects; and black hexagons, poor template fits. White hexagons represent a relative decrease in timing orincrease in amplitude; decreases in timing or increases in amplitude that exceeded 2 SDs are represented by numbers in bold underlinedtext. White hexagons also represent relative increases in timing or decreases in amplitude whose values are within 2 SD of the valuesobtained for the control subjects.

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and P10 in the macular area and decreasing them for P8. As in thecase of P1 through P4, the majority of the data points for thesepatients fell outside the range of change observed for the controlgroup. For P10, the slight increase was accompanied by a de-crease in median amplitude. When these results were comparedwith those obtained for the surrounding perimacular area (Fig. 7right), it is clear that the two regions were affected in a similarway. This increase in implicit time for P7 in the macular area wasapparent 1 month after treatment.

To assess the effects of treatment on local sensitivity,visual fields were obtained from each patient, and the differ-ences between the post- and pretreatment thresholds for alltest locations in the macular and perimacular areas were cal-culated. The results are summarized in Table 3. For patients, P1through P5, there were minimal changes in median thresholdvalues after treatment (the median change in threshold rangedfrom 0 to 20.2 log unit). Median threshold values for themacular area (for locations corresponding to the central 41hexagons in the multifocal ERG display) for patients P6through P10 also showed minimal changes after treatment (themedian change in threshold ranged from 0 to 0.2 log unit).Only one patient, P11, showed a change in threshold thatexceeded the range obtained from the seven control subjectswho were retested after 1 year. For the untreated perimacular

area, despite a greater range of threshold changes, indicatingmore variability, with the exception of P11 there was little orno change in median threshold values.

DISCUSSION

The majority of studies that have examined the effects offocal laser treatment on CSME have evaluated visual functionin the macular area using psychophysical techniques. Sev-eral studies have measured visual acuity and have showneither stabilization or improvement in acuity after focalphotocoagulation.1,13–16 More information regarding the ex-tent of retinal dysfunction has been provided by studies thathave used additional psychophysical measures of visualfunction such as threshold static perimetry, color vision, andcontrast sensitivity. These studies have reported that therewas no significant change in hue discrimination or colorconfusion,1,6,17 that contrast sensitivity showed a slight im-provement,17 and that sensitivity was either slightly de-creased (less than 4 dB) in the treated central 10° of thevisual field5,6 or was unchanged after treatment.18 In thepresent study our measures of visual acuity and local sensi-tivity in the macular and surrounding area are consistent

FIGURE 5. (A) Box and whisker plots of implicit time differences (top) and amplitude differences (bottom) for the control group and P1 throughP5. The point in the center of each box represents either the median change in implicit time in milliseconds or amplitude in microvolts for the103 responses, the box indicates the quartiles (25th and 75th percentiles), and the whiskers represent the range of values. (B) Box and whiskerplots of implicit time differences (top) and amplitude differences (bottom) for P1 and P5 obtained at 2 and at 5 months after treatment. Data areas described in (A).

IOVS, October 2000, Vol. 41, No. 11 Effects of Focal Laser Treatment on Retinal Function 3661

with the results of previous studies that have shown im-provement or stabilization of acuity and no change in theoverall sensitivity of the visual field.1,14,18

Although the results of the psychophysical tests suggestedlittle or no change in visual function, changes in retinal func-tion were observed with the multifocal ERG technique. Bothresponse timing and amplitude were affected by treatment, buttiming was more affected. For example, six of the patientsshowed increases in median implicit times in the treated mac-ular area. The question is whether these posttreatmentchanges in local ERG responses reflect local damage i.e., arethey a result of lesions produced by focal and grid photocoag-ulation or do they represent a more generalized retinal dys-function? Laser energy is absorbed primarily by the pigmentepithelium and the adjacent photoreceptor layer. Damage tothe outer retina might be expected to result in increasedimplicit times. This may account for the increased delay inimplicit times and the additional decreases in amplitude par-ticularly in the treated macular area. However, the finding forsome patients that timing changes occurred in this area and

that the surrounding retina was also affected suggests that gridphotocoagulation has a generalized effect on retinal metabo-lism.

A similar result was reported in a study of the effects oflaser treatment on PERG amplitudes.4 The decrease in PERGamplitudes after focal treatment was far larger than expected.The investigators suggested that the thermal and/or toxic ef-fects spread outside the treated area. Alternatively, other fac-tors such as residual edema, postlaser reactive edema, a pro-gression of the retinopathy and/or retinal hypoxia may havecontributed to the results.

In summary, the results presented in this study and inGreenstein et al.3 demonstrate the importance of using morethan one psychophysical or electrophysiological technique;first, to characterize the type and extent of dysfunction asso-ciated with a disease state, and second, to evaluate the out-come of treatment intervention. The approach we used allowsthe investigator to assess local retinal function and provides amethod for quantifying any changes that may occur after treat-ment.

FIGURE 6. Delay difference fields (left) and amplitude difference fields (right) for P6 (top) and P9 (bottom). The results were obtained using astimulus display subtending 47° by 39°.

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References

1. Early Treatment of Diabetic Retinopathy Study Research Group.Photocoagulation for diabetic macular edema; Early TreatmentDiabetic Retinopathy Study. Report number 1. Arch Ophthalmol.1985;103:1796–1806.

2. Early Treatment of Diabetic Retinopathy Study Research Group.Treatment techniques and clinical guidelines for photocoagulationof diabetic macular edema. Early Treatment Diabetic RetinopathyStudy. Report number 2. Ophthalmology. 1987;94:761–774.

3. Greenstein VC, Holopigian K, Hood DC, Seiple W, Carr RE. Thenature and extent of retinal dysfunction associated with diabeticmacular edema. Invest Ophthalmol Vis Sci. 2000;41:3643–3654.

4. Ciavarella P, Moretti G, Falsini B, Porciatti V. The pattern electro-retinogram (PERG) after laser treatment of the peripheral or cen-tral retina. Curr Eye Res. 1997;16:111–115.

5. Sims LM, Stoessel K, Thompson JT, Hirsch J. Assessment of visual-field changes before and after focal photocoagulation for clinicallysignificant diabetic macular edema. Ophthalmologica. 1990;200:133–141.

6. Striph GG, Hart WM Jr, Olk RJ. Modified grid laser photocoagula-tion for diabetic macular edema: the effect on the central visualfield. Ophthalmology. 1988;95:1673–1679.

7. Sutter EE, Tran D. The field topography of ERG components inman-1: the photopic luminance response. Vision Res. 1992;32:433–446.

8. Sutter EE. The fast m-transform: a fast computation of cross-corre-lations with binary m-sequences. Soc Ind Appl Math. 1991;20:686–694.

FIGURE 7. Box and whisker plots of implicit time differences (top) and amplitude differences (bottom) for the control group and for P6 throughP11 for the macular and perimacular area. Data are as in Figure 5A.

TABLE 3. Change in Threshold

SubjectsMedian

(log unit)Range

(log unit)25th Percent.

(log unit)75th Percent.

(log unit)

Macular areaControl* 0 20.3 to 0.35 20.1 0.1P1 20.2 21.2 to 1.0 20.6 0P2 0 20.4 to 0.5 20.2 0.2P3 20.1 20.6 to 0.6 20.2 0P4 0 20.7 to 0.5 20.3 0.2P5 20.15 20.6 to 0.7 20.3 0Control† 0 20.4 to 0.4 2.01 0.1P6 0.15 20.9 to 0.8 0 0.3P7 0 20.4 to 0.7 20.2 0.2P8 0 20.8 to 0.5 20.1 0.2P9 0 20.5 to 0.9 20.2 0.2P10 0.2 21.0 to 1.1 20.1 0.4P11 0.8 20.3 to 1.1 0.4 1.0

Perimaculararea

Control 0.1 20.4 to 0.4 0 0.2P6 0.2 21.3 to 1.4 0 0.4P7 0 21.0 to 0.9 20.2 0.3P8 20.2 21.5 to 1.5 20.4 0.1P9 0 21.4 to 1.4 20.4 0.2P10 0.1 21.5 to 1.5 20.2 0.4P11 0.4 20.8 to 1.2 0 0.6

* Results obtained at 58 locations in the macular area.† Results obtained at 41 locations in the macular area.

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