The effect of pseudophakia on retinal and cortical functions

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1 ORIGINAL ARTICLE The effect of seudohakia on retinal and cortical functions Fahrettin Akay 1, Fatih M. Mutlu 2, Fatih C. Gundogan 3, Gungor Sobaci 2 1 Deartment of Ohthalmology, Izmir Military Hosital, Izmir, 2 Deartment of Ohthalmology, GATA Medical Faculty, Ankara; Turkey ABSTRACT Aim To investigate the effect of seudohakia on visual electrohysiology. Methods Right eyes of 60 seudohakic (study grou) age- and sex-matched 60 hakic (control grou) volunteers were included. Subjects without any ocular and systemic disease, who had visual acuity of 9/10 underwent full-field electroretinogram (ERG), attern electroretinogram (PERG), attern visual evoked otentials (PVEP) and electro-oculogram (EOG) recordings. Corresonding author: Fahrettin Akay Deartment of Ohthalmology, Izmir Military Hosital Izmir Asker Hastanesi, Göz Hst. Servisi, İzmir, Turkey Phone: ; Fax: ; drfakay@yahoo.com Original submission: 12 March 2013; Revised submission: 07 June 2013; Acceted: 05 Setember Results The P 100 latency to 1º-check was significantly shorter in both seudohakic grous (study grou: ±6.11, control grou: ±10.70, =0.012). The P 100 amlitude to 15 -check was significantly higher in the seudohakic grous (study grou: 13.96±7.01, control grou: 11.60±4.69, : 0.033). Regarding ERG, b-wave imlicit time in rod resonse and a-wave imlicit time in standard combined resonse (SCR) were significantly shorter in the seudohakic grou (=0.017, and <0.001, resectively). B-wave amlitude in rod resonse and a-wave amlitude in SCR were significantly higher in the study grou (<0.001 for both). The P1 and N1 amlitude and imlicit time differences in 30-Hz flicker resonse were not significant (>0.05). Conversely, P3/P4 imlicit times in oscillatory otentials (OPs) were delayed in the seudohakic grou (=0.001, and 0.002, resectively). The P1 amlitude increase in OPs in the study grou was significant (<0.001). The N 95 latency in PERG was significantly delayed (=0.002) and P50 amlitude was increased (=0.002) in the seudohakics. Arden ratio in EOG was similar in both grous (=0.961). Conclusion Pseudohakia seems to influence ocular electrohysiological tests. Possible causes of these influences in the atients with seudohakia should be clarified by further studies. Key words: electrooculogram, electroretinogram, attern electroretinogram, attern visual evoked otentials Med Glas (Zenica) 2014; 11(1):

2 Akay et al. Pseudohakia and electrohysiology INTRODUCTION The elderly oulation is increasing throughout the world, and senile cataract is the leading cause of reventable blindness all over the world (1). Recent develoments in cataract surgery have increased the number of seudohakic eole throughout the world (2). Ocular electrohysiological tests are widely used diagnostic methods and with time, an increasing number of seudohakic atients are undergoing quantitative electrohysiological tests esecially to detect and follow u glaucoma, retinal and neuroohthalmological diseases (3). For this reason, it would be of great value to have more recise information on the effect of seudohakia on the results of electrohysiological tests (4). A number of studies investigated the effect of different degrees of cataract on ocular electrohysiological tests on a re-and ost-oerative basis (5-9). Cataract was shown to reduce the amlitudes of the a-wave and the b-wave of the scotoic full-field electroretinogram (ERG) (4). In contrast, a normal (10) and a larger (3) than normal scotoic ERG resonse have also been recorded in atients with cataract. It was suggested that the latter effect might be due to the light-scattering effect of the cataract (3). Chan et al found that the central multifocal electroretinogram (mferg) resonse density was reduced, but the eriheral mferg resonse densities were increased under the light scattering condition (11). Cataract was also shown to reduce attern electroretinogram (PERG) amlitude and delay attern visual evoked otential (PVEP) latency (5,6). To our knowledge, there has been no study that investigated the influence of seudohakia on human ocular electrohysiology although this toic has eidemiological imortance. The aim of this study was to exlore the effect of seudohakia on PVEP, PERG, full-field electroretinogram (ERG) and electrooculogram (EOG). PATIENTS AND METHODS This rosective, case-control study was conducted in a tertiary health center in Turkish Army. In agreement with the Declaration of Helsinki, aroval from the Ethics Committee had been obtained and articiants had given their informed consents in writing. The right eyes of 60 consecutive atients with bilateral seudohakia (study grou) and 60 volunteers with bilateral hakia (control grou) were included. Extracasular cataract extraction (hacoemulsification) and osterior chamber intraocular lens (Sensar AR40e, AMO) imlantation was erformed by a single exerienced surgeon (FMM). Posterior casule remained intact in all oerated atients. In order to revent a ossible retinal hototoxicity due to oerating microscoe, the oerations were erformed at low illumination setting. Only right eyes of those atients with the final best corrected visual acuity (BCVA) of 9/10 or better were included. The tye and degree of lens oacification of the hakic subjects who were willing to articiate in the study were evaluated by the same ohthalmologist (FMM) with dilated uils and only the subjects with clear lenses (N0, NC0 or 1, C0, P0, Lens Oacities Classification System II) were included in the study in order to minimize the influence of cataract on electrohysiological tests. In either atients or subjects, inclusion criteria were the absence of clouding of the otic media, other eye disease such as glaucoma, age-related macular degeneration, high myoia or systemic diseases that might affect the tests, such as diabetes mellitus and systemic arterial hyertension. To ensure that all subjects were free of retinal disease, eye examination including measurement of visual acuity, intraocular ressure, slit-lam and fundoscoic examinations was done. In addition, fast macular thickness analysis rocedure by using otical coherence tomograhy-internal normative database (OCT Stratus, Zeiss) was erformed in seudohakic subjects in order to exclude macular edema. All subjects had less than ±2 D of sheric error and less than 1.00 D of astigmatism. Electrohysiological tests were erformed at least 6 months after the surgery. Electrohysiological tests The Roland-Consult RetiPORT System (Wiesbaden, Germany) was used. All recordings were made on the basis of the International Society for Clinical Electrohysiology of Vision (ISCEV) recommendations (12-15). The room temerature was 21 C and, background illumination was below 1 cd/m 2 in all recordings. 121

3 Medicinski Glasnik, Volume 11, Number 1, February 2014 Electroretinogram The electroretinogram (ERG) is a total resonse for the whole retina to hotoic stimuli and the record of the action otential generated at that time. The ERG reresents the combined electrical activity of different cells in the retina. A standard ERG includes recording of the rod resonse, standard combined resonse, oscillatory otentials (OPs), single flash cone resonse and 30-Hz flicker cone resonse (12). Puil dilation was erformed by instilling one dro of troicamide 1%. To record rod ERG, SCR and OPs, all subjects were dark adated for 30 minutes. Dawson-Trick-Litzkow (DTL) fiber electrodes were then ositioned rior to recording under dim red light. A white flash of cds/m 2 (25 log units below the standard flash of 3.00cds/m 2 ) was used with an interval of 2s to obtain rod ERG. To record SCR and OPs, white standard flash (3.00cds/m 2 ) was used with an interval of 10 s and 2 s, resectively. Subjects were than light adated to a white rod saturating background (25 cd/m 2 ) for 10-min before recording cone and 30-Hz flicker resonses by white standard flash. The interval between the stimuli in recording single flash cone ERG was 2s. The resonses were amlified with a gain of and recorded over a bandwith of Hz for OPs and Hz for rod, SCR, single flash cone ERG and 30-Hz flicker ERG recordings. A tyical ERG recording is shown in Figure 1. Pattern visual evoked otential (PVEP) The PVEP is a cortical resonse to a contrastreversal of a checkerboard attern. PVEP comonents that are commonly measured include the N 75, P 100, and N 135 (Figure 1). P 100 eak is the most stable eak between the subjects and it is the most useful arameter in clinical evaluations. Refractions of the subjects were corrected before the PVEP recordings with trial lenses. Monocular PVEPs were recorded with gold disc surface electrodes. Active electrodes were laced on the scal over the visual cortex at Oz with the reference electrode at Fz. The ground electrode was laced on the forehead. A 20 cm x 30 cm screen was laced 1 meter in front of the subjects. The reversal rate was 2 reversals er second. One hundred stimuli were averaged. The checkerboard stimulus Figure 1. Electroretinogram, attern visual evoked otentials, attern electroretinogram and electro-oculogram recorded from a articiant subtended a visual angle of 5.7 vertically and 8.5 horizontally on either side of the fixation. Luminance was <1 cd/m 2 (<0.017cds/m 2 ) for black hexagons and 115 cd/m 2 (1.92 cds/m 2 ) for the white hexagons (contrast: 99%). The PVEP recordings to two check sizes (1º, 15 ) were obtained. Pattern electroretinogram (PERG) The PERG is the retinal resonse to a structured stimulus, such as a reversing black-and white checkerboard or grating. The PERG is a small resonse, and its recording is technically more demanding than other visual electrohysiologic tests. The waveform consists of a rominent ositive comonent, P 50, with a larger later negative comonent, N 95 (Figure 1). Refractions of the subjects were corrected before the recordings with trial lenses. Monocular PER- Gs (right eye) were recorded with DTL fiber electrodes. The electrodes were laced in the lower fornix and stabilized near the lateral canthus with adhesive stris. Gold cu reference electrodes were laced at the isilateral outer canthi. A ground electrode was attached to the forehead. The electrical imedance for all electrodes was less than 3 kω. The contrast level, reversal rate and 122

4 Akay et al. Pseudohakia and electrohysiology RESULTS The difference for age, sex, best-corrected visual acuity and refraction was not significant between the grous (Table 1). Table 1. Demograhic and clinical characteristics of the Figure 2. Pattern electroretinogram P50 and N95 amlitudelatency comarison between seudohakic and hakic articiants check size were 99% (with the same luminance levels used for PVEP recording), 3 reversals er second (transient PERG). Only one check size (30 ) was used. The filter was set at Hz. One hundred and fifty stimuli were averaged. Fixation was monitored closely by an exerienced electrohysiology technician during PVEP and PERG recordings. Electrooculogram (EOG) The EOG records a standing or resting otential of aroximately 6mV that is always resent between the cornea and the back of the eye. The current flow is oriented so that voltage at the cornea is ositive relative to the osterior ole. Gold cu skin electrodes were attached with tae near the lateral and medial canthi of both eyes to record EOG. Puil dilation with 1% troicamide was erformed. Horizontal fixation targets were 30 degrees aart. After the initial re-adatation eriod of 15-min in room light, all lights were turned off and resonses from saccadic eye movements were recorded for 15-min under a darkadated condition (<1 cd/m 2 ) and for 15-min under the light adated (100 cd/m 2 ) hase. Time interval of stimulation was 60s. The EOG data was collected for the first 12 s of every minute. The ratio of light eak to dark through (Arden ratio) was determined to evaluate the difference between the grous. Statistical analysis The difference between the data in the grous was investigated using indeendent samles t test. Indeendent samles t-test and chi-square tests were used to exlore statistical significance for the variables in electrohysiologic tests and gender differences between the grous, resectively. Characteristics seudohakia hakia Age (years) 69.4± ± Sex (Male/Female) (No) 30/30 32/ BCVA (metric values) 0.94± ± Refraction (dioters) -0.41± ± BCVA, best corrected visual acuity P 100 latency in 1 -check was significantly delayed in subjects with hakia comaring to the atients with seudohakia (=0.012). In addition, P100 amlitude in 15º-check was almost significantly reduced in subjects with hakia (=0.061) (Table 2). Table 2. P 100 amlitude and latency differences between the atients with seudohakia and hakia Parameters P100 amlitude (µv) P100 latency (ms) Check size seudohakia hakia 1º 11.8± ± ± ± º 103.0± ± ± ± B-wave imlicit time in rod resonse, a-wave imlicit time in SCR were significantly shorter in the atients with seudohakia. In addition, b-wave amlitude in rod resonse, a-wave amlitude in SCR, and a-wave amlitude in single cone resonse was significantly higher in the study grou (Table 3). Regarding the OPs, there was significant delay in imlicit times for P 3 and P 4 waves in the study grou. In addition, the atients with seudohakia had significantly higher P 1 amlitude in the OPs (Table 4). Table 3. Electroretinogram differences between the atients with seudohakia and hakia Rod resonse Standard combined resonse Cone resonse 30-Hz flicker resonse Parameters seudohakia Patients with hakia b wave (ms) 78.8± ± b wave (µv) 88.1± ±13.2 <0.001 a wave (ms) 18.9± ±1.7 <0.001 b wave (ms) 44.5± ± a wave (µv) 121.6± ±22.5 <0.001 b wave (µv) 200.5± ± a wave (ms) 15.5± ± b wave (ms) 33.5± ± a wave (µv) 20.1± ±4.5 <0.001 b wave (µv) 70.0± ± N1 (ms) 14.2± ± P1 (ms) 29.0± ± P1 (µv) 61.7± ± Hz (µv) 23.4± ±

5 Medicinski Glasnik, Volume 11, Number 1, February 2014 Table 4. Oscillatory otential differences between the atients with seudohakia and hakia Parameters OP1 OP2 OP3 OP4 The significant differences in PERG between the grous were observed in N 95 imlicit time and P 50 amlitude. N 95 imlicit time was delayed and P 50 amlitude was higher in the study grou (Figure 2). N 95 /P 50 ratio was significantly lower in the atients with seudohakia (2.01±0.17), comaring to the atients with hakia (1.88±0.23) (<0.001). The Arden ratios in the study grou and control grou were 2.368±0.431 and 2.381±0.522, resectively. The difference was not significant (=0.961). DISCUSSION seudohakia hakia Amlitude (µv) 22.7± ±4.5 <0.001 Imlicit time (ms) 19.6± ± Amlitude (µv) 44.6± ± Imlicit time (ms) 26.6± ± Amlitude (µv) 7.2± ± Imlicit time (ms) 36.8± ±1.3 <0.001 Amlitude (µv) 6.3± ± Imlicit time (ms) 50.9± ± Cataract extraction and IOL imlantation is currently the only way for the treatment of cataract, the most significant cause of reventable blindness over the world (16). Although most IOLs rovide a reasonable imitation of the sectral characteristics of the natural human lens, the balance is a little less otimal than in the natural lens (17). A study showed that VEPs recorded on the first day after removal of a longstanding, dense, unilateral cataract showed a marked delay to stimulation of the oerated eye comared to the unoerated eye, delays in the VEP returned to normal within aroximately 3 months after the surgery, suggesting the sensitiveness of the adult central visual system to visual derivation caused by longstanding, dense cataract (6). Semenicki et al. (18) observed a shortening of the N 2 latency of flash VEP after cataract extraction and IOL imlantation. To the best of our knowledge, there has been no study that investigated the PVEP difference between the seudohakic subjects and age- and sex-matched controls. Cataract decreases the contrast of the objects on the retina (19). For this reason, the latency shortening after cataract extraction that was found in revious studies is rather logical (6, 18). However, in this study, we showed that there was still a significant shortening of P 100 latency in the seudohakics with resect to age-matched hakics, even after at least 6 months of cataract surgery. Although the mean age of both atient grous in the resent study was similar, a slightly significant decrease in contrast ercetion due to age-related changes of the lens of hakic subjects may cause this difference. However, this assumtion needs to be confirmed. A second ossible cause for PVEP and also ERG results according to the results of the resent study may be related to the light scattering effect of intraocular lenses. A study showed that intraocular light scatter in seudohakic eyes increase by a factor of 2 with resect to age-matched normal eyes (20). Light scattering by the intraocular lens causes the stimulation of a retinal area many times, and this may result in amlitude increase and latency shortening in ERG and PVEP. The suranormal ERG amlitude increase and latency shortening in ocular albinism are also caused by this mechanism (21). The results of this study have shown that OPs were a series of wavelets suerimosed on the ascending limb of the ERG b-wave after stimulation by an intense light flash. The cellular origin of OPs in the retina is somewhat uncertain (22). Current information suorts the conclusion that cells of the inner retina sulied by the retinal circulation, such as the amacrine or ossibly interlexiform cells, are the generators of these otentials (23, 24). Reduction of amlitude of OPs becomes aarent in atients with diabetic retinoathy, central retinal vein occlusion, sickle cell retinoathy, X-linked juvenile retinoschisis, and in some atients with congenital stationary night blindness (25). This study found significantly delayed imlicit times (P 3, P 4 ) and lower P 1 amlitude in OPs in the seudohakic grou. This result may be interreted as reduced OPs in the seudohakic subjects. The PERG is a owerful clinical tool, allowing both an objective evaluation of macular function and a direct assessment of retinal ganglion cell function. P 50 and N 95 may be selectively affected in macular and otic nerve (and ganglion cell) disease, resectively (26, 27). Previous studies showed that chemical mediators such as, cytokines and rostaglandins, increase in the 124

6 Akay et al. Pseudohakia and electrohysiology intraocular environment after hakoemulsification surgery and this results in the disrution of blood-aqueous and blood-retina barrier (28). The athohysiology of the ostoerative cystoid macular edema is exlained with this theory (29). In addition, it is robable that these chemical mediators affect not only the macula but also may affect the eriheral retina (28). Suorting this assumtion, Teresaki et al (30) reorted significant amlitude reductions and imlicit time delay in OPs in atients with ahakic and seudohakic cystoid macular edema. The atients in this study had neither cystoid macular edema nor increased macular thickness with resect to normative OCT database, but we had reduced OPs and N 95 latency delay in seudohakic atients. These PERG and OPs results may show an irreversible or long-lasting functional imairment in the inner retina due to intraocular inflammation after the hakoemusification surgery. There are various reorts describing retinal and macular changes, remaining stable for at least 6 months after cataract surgery (31, 32). The effect of cataract surgery on retinal and macular functions needs to be clarified by retinal electrohysiological and structural studies. The EOG resonse has two comonents: one light-insensitive other light-sensitive. It is a widely used test which measures the light resonse of the retinal igment eithelium, but it is not a ure test of RPE function since retinal hotorecetion is required in the light-sensitive comonent (33). The light-insensitive comonent deends on the integrity of the retinal igment eithelium. This comonent, accounting for the dark through, is not influenced by revious retinal illumination and it is thus indeendent of the functional status of the retinal hotorecetors (33). The light sensitive comonent aears to be generated by a deolarization of the basal membrane of the RPE (34). Intact hotorecetor cells are, however, also necessary to generate this resonse (33, 35). Arden ratio difference between the seudohakic and hakic subjects in this study was not significant. This insignificant EOG difference between the grous may mean that the ossible functional imairment in the inner retina because of the increased inflammatory mediators may ossibly not affect the outer retina (or retinal igment eithelium) In conclusion, significant differences in ERG, PVEP and PERG resonses in seudohakics may ossibly be related to the differences in otical erformance of IOLs and natural human lens or the inflammatory resonse of ocular tissues after cataract surgery. However, further studies are necessary to clarify ossible causes of the influence of seudohakia on electrohysiological tests. FUNDING No secific funding was received for this study. TRANSPARENCY DECLARATIONS Cometing interests: None to declare. REFERENCES 1. Thylefors B, Negrel AD, Pararajasegaram R, Dadzie KY. Global data on blindness. Bull World Health Organ 1995; 73: Heijl A, Leske MC. Cataract eidemiology. Ohthalmology 2007;114: Galloway NR. Electrohysiological testing of eyes with oaque media. Eye (Lond) 1988; 2: Hurst MA, Douthwaite WA. Assessing vision behind cataract--a review of methods. Otom Vis Sci 1993; 70: Howe JW, Mitchell KW, Mahabaleswara M, Abdel- Khalek MN. Visual evoked otential latency and contrast sensitivity in atients with osterior chamber intraocular lens imlants. Br J Ohthalmol 1986; 70: Sloer JJ, Collins AD. Delayed visual evoked otentials in adults after monocular visual derivation by a dense cataract. Invest Ohthalmol Vis Sci 1995; 36: Andreassi JL, Zalkind SS, Gallichio JA, Young NE. Monocular and binocular visual evoked otentials before and after cataract surgery. Percet Mot Skills 1979; 49: Mauck K, Dodt E, Schnaudigel OE, Ohrloff C. Effect of cataracts on contrast attern reversal stimuli exemlified by the attern electroretinogram. Ohthalmologe 1996; 93: Wordehoff UV, Palmowski AM, Heinemann-Vernaleken B, Allgayer R, Rurecht KW. Influence of cataract on the multifocal ERG recording--a re- and ostoerative comarison. Doc Ohthalmol 2004; 108: Cruz RD, Adachi-Usami E. Quantitative evaluation of electroretinogram before cataract surgery. Jn J Ohthalmol 1989; 33: Chan HL, Siu AW, Ya MK, Brown B. The effect of light scattering on multifocal electroretinograhy. Ohthalmic Physiol Ot 2002; 22:

7 Medicinski Glasnik, Volume 11, Number 1, February Marmor MF, Holder GE, Seeliger MW, Yamamoto S, International Society for Clinical Electrohysiology of V. Standard for clinical electroretinograhy (2004 udate). Doc Ohthalmol 2004; 108: Odom JV, Bach M, Barber C, Brigell M, Marmor MF, Tormene AP, Holder GE, Vaegan. Visual evoked otentials standard (2004). Doc Ohthalmol 2004; 108: Bach M, Hawlina M, Holder GE, Marmor MF, Meigen T, Vaegan, Miyake Y. Standard for attern electroretinograhy. International Society for Clinical Electrohysiology of Vision. Doc Ohthalmol 2000; 101: Marmor MF, Zrenner E. Standard for clinical electro-oculograhy. International Society for Clinical Electrohysiology of Vision. Doc Ohthalmol 1993; 85: Richter GM, Chung J, Azen SP, Varma R, Los Angeles Latino Eye Study Grou. Prevalence of visually significant cataract and factors associated with unmet need for cataract surgery: Los Angeles Latino Eye Study. Ohthalmology 2009; 116: Van Norren D, van de Kraats J. Sectral transmission of intraocular lenses exressed as a virtual age. Br J Ohthalmol 2007; 91: Semenicki K, Ciszewska J, Kosicka J. Visual evoked otentials in seudohakia. Klin Oczna 1990; 92: Werner JS, Peterzell DH, Scheetz AJ. Light, vision, and aging. Otom Vis Sci 1990; 67: Witmer FK, van den Brom HJ, Kooijman AC, Blanksma LJ. Intra-ocular light scatter in seudohakia. Doc Ohthalmol 1989; 72: Russell-Eggitt I, Kriss A, Taylor DS. Albinism in childhood: a flash VEP and ERG study. Br J Ohthalmol 1990; 74: Janaky M, Gouland SG, Benedek G. Human oscillatory otentials: comonents of rod origin. Ohthalmologica 1996; 210: Miyake Y. Macular oscillatory otentials in humans. Macular OPs. Doc Ohthalmol 1990; 75: Heynen H, Wachtmeister L, van Norren D. Origin of the oscillatory otentials in the rimate retina. Vision Res 1985; 25: Wachtmeister L. Oscillatory otentials in the retina: what do they reveal. Prog Retin Eye Res 1998; 17: Schuurmans RP, Berninger T. Luminance and contrast resonses recorded in man and cat. Doc Ohthalmol 1985; 59: Kirkham TH, Couland SG. The attern electroretinogram in otic nerve demyelination. Can J N28. Findl O, Amon M, Petternel V, Kruger A. Early objective assessment of intraocular inflammation after hacoemulsification cataract surgery. J Cataract Refract Surg 2003; 29: Miyake K, Mibu H, Horiguchi M, Shirasawa E. Inflammatory mediators in ostoerative ahakic and seudohakic baboon eyes. Arch Ohthalmol 1990; 108: Terasaki H, Miyake K, Miyake Y. Reduced oscillatory otentials of the full-field electroretinogram of eyes with ahakic or seudohakic cystoid macular edema. Am J Ohthalmol 2003; 135: Perente I, Utine CA, Ozturker C, Cakir M, Kaya V, Eren H, Karan Z, Yilmaz OF. Evaluation of macular changes after uncomlicated hacoemulsification surgery by otical coherence tomograhy. Curr Eye Res 2007; 32: Lobo CL, Faria PM, Soares MA, Bernardes RC, Cunha-Vaz JG. Macular alterations after small-incision cataract surgery. J Cataract Refract Surg 2004; 30: Arden GB, Constable PA. The electro-oculogram. Prog Retin Eye Res 2006; 25: Steinberg RH, Linsenmeier RA, Griff ER. Three light-evoked resonses of the retinal igment eithelium. Vision Res 1983; 23: Arden GB, Wolf JE. The human electro-oculogram: interaction of light and alcohol. Invest Ohthalmol Vis Sci 2000; 41: