Combined meropenem and linezolid as a systemic treatment for postoperative endophthalmitis.

PURPOSE: The aim of this study was to evaluate the antibiotic treatment of postoperative endophthalmitis with combined systemic meropenem and linezolid. METHODS: A retrospective analysis of endophthalmitis treated with systemic meropenem and linezolid compared to conventional systemic antibiotics by evaluation of outcome and adverse effects was carried out. RESULTS: 26 patients with unilateral postoperative endophthalmitis with a systemic combination regimen of meropenem (2 g TID, mean duration of treatment 5.5 days) and linezolid (600 mg BID, mean duration of treatment 8.9 days) (group 1, mean follow-up time 140 days) were included in this study and compared to 45 postoperative endophthalmitis patients treated with conventional systemic antibiotics (group 2; mean follow-up time 320 days). In group 1, 69.2 % of eyes additionally received intravitreal amikacin and vancomycin (vs. 24.4 % in group 2; p < 0.001), in 92.3 % pars plana vitrectomy was performed (vs. 68.9 % in group 2, p = 0.047). Mean best corrected visual acuity improved from a baseline of 1.76 logMar for group 1 and 1.83 logMar for group 2 to 0.91 logMar (p = 0.0001) and 0.90 logMar (p < 0.0001), respectively, at the end of the follow-up, revealing no significant differences between the two groups at any time point (p > 0.05). Ocular complications were observed in 34.6 % of eyes in group 1 (vs. 37.8 % in group 2; p > 0.05). Adverse drug effects occurred significantly more frequently in group 1 (26.9 % vs. 4.4 % p = 0.02). CONCLUSION: In spite of the reported better penetration through the blood-ocular barrier and the broader antibacterial spectrum of meropenem and linezolid, no benefit in outcome was found in the present study. In contrast, adverse effects and costs of the combination regimen were significantly higher.

[Photodynamic therapy of AMD for the first (better sight) and the second (worse sight) eyes]. / Photodynamische Therapie bei altersbedingter Makuladegeneration am schlechteren und besseren Auge.

BACKGROUND: Photodynamic therapy (PDT) is the standard treatment procedure for many forms of exudative and/or neovascular AMD. Despite therapy, visual acuity often drops to low vision levels. The cost efficiency of treating the eye in which vision is worse is therefore the subject of some controversy. PATIENTS AND METHODS: A retrospective case-control study was conducted in all patients who were treated with PDT at the Universitätsspital Zürich between September 1999 and November 2004. Each patient's first (with worse vision) and second (with better vision) eyes were compared for situation on presentation and course during treatment. RESULTS: In 117/228 cases (51.3%) visual acuity of the treated eye was better than (or identical to) that of the fellow eye at presentation. Visual acuity before therapy was an average of 0.58+/-0.27 logMAR [Snellen: 0.26 (0.14-0.49)] in the eyes with better visual acuity and 0.69+/-0.4 logMAR [Snellen 0.20 (0.08-0.51)] in the fellow eyes (p=0.015). After therapy there was no significant difference between the patient groups in visual acuity or in the magnitude of any change in visual acuity, or in lesion size or change in lesion size. CONCLUSION: The outcome of PDT of a second eye (with better visual acuity) is not significantly better than the result obtained in the first eye (the one with worse visual acuity initially).

NO/cGMP pathway activation and membrane potential depolarization in pig ciliary epithelium.

PURPOSE: To investigate whether in isolated porcine ciliary processes, stimulation of the nitric oxide (NO)-guanylate cyclase (GC)-3',5'-cyclic guanosine monophosphate (cGMP) pathway modulates ciliary epithelial transmembrane potential. METHODS: Changes in transmembrane potential induced by the two NO donors, sodium nitroprusside (SNP; 100 microM) and S-nitroso-N-acetyl-penicillamine (SNAP; 100 microM), or by the cGMP-analogue 8-para-chlorophenylthioguanosine-3', 5'-cyclic guanosine monophosphate (8-pCPT-cGMP; 100 microM) were measured with microelectrodes in the presence or in the absence of the GC-inhibitor 1-H-(1,2,4)oxadiazole(4,3-alpha)quinoxalin-1-1 (ODQ; 10 microM). The effect of 8-pCPT-cGMP was also assessed in the presence of the anion channel inhibitors niflumic acid (100 microM), diisothiocyanatostilbene-2,2' disulfonic acid (DIDS; 1 mM), anthracene-9-carboxylic acid (9-AC; 1 mM), or the K+ channel blocker tetraethylammonium chloride (TEA; 10 mM). cGMP production was measured by immunoassay. RESULTS: Significant membrane depolarizations (P < 0.05-0.001; n = 5-8) were induced by SNP (6 +/- 1 mV; mean +/- SEM), SNAP (8 +/- 1 mV), or 8-pCPT-cGMP (13 +/- 1 mV). In presence of ODQ, the effect of SNP and SNAP were significantly inhibited (-2 +/- 0 mV and 0 +/- 0 mV, respectively; P < 0.05; n = 5-6), but not depolarizations elicited by 8-pCPT-cGMP. These were prevented (P < 0.05-0.01; n = 5) by niflumic acid (1 +/- 1 mV), DIDS (1 +/- 1 mV), or 9-AC (5 +/- 1 mV), but not by TEA (12 +/- 2 mV). The increase in cGMP production induced by SNP (9.5-fold) was inhibited by ODQ (P < 0.001; n = 6). CONCLUSIONS: Activation of the NO-GC-cGMP pathway modulates epithelial transmembrane potential in isolated porcine ciliary processes.

The potential effect of population development, smoking and antioxidant supplementation on the future epidemiology of age-related macular degeneration in Switzerland.

BACKGROUND: Due to the predicted age shift of the population an increase in the number of patients with late AMD is expected. At present smoking represents the only modifiable risk factor. Supplementation of antioxidants in patients at risk is the sole effective pharmacological prevention. The aim of this study is to estimate the future epidemiological development of late AMD in Switzerland and to quantify the potential effects of smoking and antioxidants supplementation. METHODS: The modelling of the future development of late AMD cases in Switzerland was based on a meta-analysis of the published data on AMD-prevalence and on published Swiss population development scenarios until 2050. Three different scenarios were compared: low, mean and high. The late AMD cases caused by smoking were calculated using the "population attributable fraction" formula and data on the current smoking habits of the Swiss population. The number of potentially preventable cases was estimated using the data of the Age-Related Eye Disease Study (AREDS). RESULTS: According to the mean population development scenario, late AMD cases in Switzerland will rise from 37 200 cases in 2005 to 52 500 cases in 2020 and to 93 200 cases in 2050. Using the "low" and the "high" scenarios the late AMD cases may range from 49 500 to 56 000 in 2020 and from 73 700 to 118 400 in 2050, respectively. Smoking is responsible for approximately 7 % of all late AMD cases, i. e., 2600 cases in 2005, 3800 cases in 2020, 6600 cases in 2050 ("mean scenario"). With future antioxidant supplementation to all patients at risk another 3100 cases would be preventable until 2020 and possibly 23 500 cases until 2050. CONCLUSION: Due to age shift in the population a 2.5-fold increase in late AMD cases until 2050 is expected, representing a socioeconomic challenge. Cessation of smoking and supplementation of antioxidants to all patients at risk has the potential to reduce this number. Unfortunately, public awareness is low. These data may support health-care providers and public opinion leaders when developing public education and prevention strategies.

Comparison of tendency-oriented perimetry and dynamic strategy in octopus perimetry as a screening tool in a clinical setting: a prospective study.

OBJECTIVE: The aim of this study was to compare the results of tendency-oriented perimetry (TOP) and a dynamic strategy in octopus perimetry as screening methods in clinical practice. DESIGN: A prospective single centre observational case series was performed. PARTICIPANTS AND METHODS: In a newly opened general ophthalmologic practice 89 consecutive patients (171 eyes) with a clinical indication for octopus static perimetry testing (ocular hypertension or suspicious optic nerve cupping) were examined prospectively with TOP and a dynamic strategy. The visual fields were graded by 3 masked observers as normal, borderline or abnormal without any further clinical information. RESULTS: 83% eyes showed the same result for both strategies. In 14% there was a small difference (with one visual field being abnormal or normal, the other being borderline). In only 2.9% of the eyes (5 cases) was there a contradictory result. In 4 out of 5 cases the dynamic visual field was abnormal and TOP was normal. 4 of these cases came back for a second examination. In all 4 the follow-up examination showed a normal second dynamic visual field. CONCLUSIONS: Octopus static perimetry using a TOP strategy is a fast, patient-friendly and very reliable screening tool for the general ophthalmological practice. We found no false-negative results in our series.

Comparison of performance and patient satisfaction of two types of ERG electrodes.

BACKGROUND: An age-controlled comparison concerning patient satisfaction and electrical performance of microfibres (DTL) and rigid contact lens (Henkes) corneal ERG electrodes was carried out. METHODS: 36 test persons underwent complete ophthalmological examination and were equally distributed into 3 age groups. Electroretinograms were recorded according to ISCEV standards. Randomly, in one eye a Henkes electrode was used and in the other eye a DTL electrode. Amplitudes of a- and b-waves and implicit times were measured and compared for the two electrode types. RESULTS: 34 of 36 test persons preferred DTL electrodes. Electrical performance concerning b-wave amplitudes was comparable. Statistically significant differences were detected only for scotopic combined cone-rod stimulation in the age groups 20 - 40 and 41 - 60 years between the different electrodes. Other recordings did not show differences. A statistically significant reduction of signal amplitudes with age was detected for scotopic isolated rod signals and combined cone-rod signals. Significance level was p < 0.05. No conjunctival or corneal erosions were found after ERG recordings for either electrode. CONCLUSIONS: Electrical performance is comparable between electrodes. For scotopic stimulations age was a significant influencing factor for signal amplitude and should be respected for normative values. DTL electrodes were preferred by the vast majority of patients. No adverse clinical effects were observed for either electrode. DTL electrodes should be preferred due to hygienic reasons (single use) and patient comfort.

Intravitreal triamcinolone acetonide for serous retinal pigment epithelial detachments in exudative age-related macular degeneration.

BACKGROUND: Due to the high risk of RPE tears PDT is usually not performed in eyes with serous RPE detachments (sRPED). For this reason this subform of exudative AMD was so far untreatable. PATIENTS AND METHODS: We report on a prospective uncontrolled observational case series. 20 eyes of 20 patients with subfoveal sRPED demonstrated by OCT were treated between June 2005 and April 2006 with intravitreal triamcinolone acetonide (IVTA). In 15 cases there was a primary sRPED, in 5 cases it had developed after one or more sessions of photodynamic therapy with Visudyne. RESULTS: There was a trend for better average visual acuity in the group with primary sRPED from 0.73 logMAR (0.19 Snellen equivalent) at baseline (n = 15) to 0.68 logMAR (0.21 Snellen) after one month (n = 15) (p = 0.19) and to 0.60 logMAR (0.25 Snellen) after three months (n = 14) (p = 0.41). The maximal height of sRPED decreased to an average of 35.3 % after one month (n = 15) and increased again to 56.9 % after 3 months (n = 14). One patient was lost to follow-up. In the group of eyes with sRPED after PDT, one eye developed an RPE tear with severe vision loss two weeks after IVTA. In the remaining four eyes average visual acuity improved from 0.90 logMAR (0.13 Snellen) at baseline to 0.73 logMAR (0.19 Snellen) after one month and to 0.80 logMAR (0.16 Snellen) after 3 months. Complete resolution of sRPED was observed in 8/20 eyes (4/5 eyes with sRPED after PDT and 4/15 eyes with primary sRPED). CONCLUSIONS: IVTA seems to be a therapeutic option in otherwise untreatable eyes with sRPED.

First clinical experience with anecortave acetate (Retaane).

BACKGROUND: Anecortave acetate is an angiostatic cortisene which is injected as a posterior juxtascleral depot and has been shown to be effective in the treatment of exudative age-related macular degeneration (AMD). The compound is not yet approved in Switzerland but can be used as "compassionate use" in individual cases. PATIENTS AND METHODS: An uncontrolled case series with standardised documentation of ETDRS visual acuity, near acuity, need for magnification and fluorescein angiography was performed. RESULTS: 22 eyes of 19 patients (8 male, 11 female, average age 78.8 years) were treated with a posterior juxtascleral depot injection (PJD) of 15 mg anecortave acetate. The mean change in visual acuity after 3 months in eyes treated with anecortave acetate was -2.6 ETDRS letters corresponding to 0.52 Snellen lines. 3/20 eyes gained more than 1 line. 11/20 eyes showed stable visual acuity (+/- 1 Snellen line, +/- 5 ETDRS letters). 5/20 eyes developed moderate vision loss (one to two Snellen lines, 6-10 ETDRS letters). 1/20 lost 18 ETDRS letters (> 3 Snellen lines). There were no moderate or severe adverse events. CONCLUSIONS: A PJD of 15 mg anecortave acetate is safe and well tolerated. In eyes with occult CNV without recent progression or with residual neovascular activity after photodynamic therapy anecortave acetate may be an alternative therapeutic option before considering intravitreal anti-VEGF agents due to the much less invasive character and lower risk profile.

[Does cataract surgery increase the risk of exudative age-related macular degeneration? Results from a large retrospective case-control study]. / Besteht ein Zusammenhang zwischen einer Kataraktoperation und nachfolgender exsudativer altersbedingter Makuladegeneration? Eine grosse retrospektive Fallkontrollstudie.

BACKGROUND: Many epidemiological studies indicate a positive correlation between cataract surgery and the subsequent progression of age-related macular degeneration (AMD). Such a correlation would have far-reaching consequences. However, in epidemiological studies it is difficult to determine the significance of a single risk factor, such as cataract surgery. PATIENTS AND METHODS: We performed a retrospective case-control study of patients with new onset exudative age-related macular degeneration to determine if cataract surgery was a predisposing factor. A total of 1496 eyes were included in the study: 984 cases with new onset of exudative AMD and 512 control eyes with early signs of age-related maculopathy. Lens status (phakic or pseudophakic) was determined for each eye. RESULTS: There was no significant difference in lens status between study and control group (227/984 [23.1 %] vs. 112/512 [21.8 %] pseudophakic, p = 0.6487; OR = 1.071; 95 % CI = 0.8284-1.384). In cases with bilateral pseudophakia (n = 64) no statistically significant difference of the interval between cataract surgery in either eye and the onset of exudative AMD in the study eye was found (225.9 +/- 170.4 vs. 209.9 +/- 158.2 weeks, p = 0.27). CONCLUSIONS: Our results provide evidence that cataract surgery is not a major risk factor for the development of exudative AMD.

In glaucoma, should enthusiasm about neuroprotection be tempered by the experience obtained in other neurodegenerative disorders?

Some in vitro and in vivo evidence, as well as rare observations in human eyes with glaucoma, suggests that retinal ganglion cells could be lost by apoptosis during the course of glaucomatous optic neuropathy. There exist also observations indicating that in the vitreous of patients with glaucoma it is possible to measure an increased concentration of glutamate (an excitotoxic amino acid known to induce neuronal apoptosis in animal models). These observations, among others, suggest the possibility of an excitotoxicity mechanism in the pathogenesis of glaucoma and as a consequence the potential for a neuroprotective approach to treating this disorder. Amazingly, not only in glaucoma but also in other neurodegenerative disorders (Parkinson's disease, amyotrophic lateral sclerosis, stroke, etc.) it has been postulated that neurons could be lost through an excitotoxic mechanism. In these non-glaucomatous disorders, quite a large number of clinical trials have already been conducted to determine the potential benefit of different neuroprotective therapies. Unfortunately, with a few rare exceptions, the results of these clinical studies have been very disappointing (in contrast to encouraging results obtained in preclinical trials). The experience acquired in other neurodegenerative disorders should probably be kept in mind when addressing the question of neuroprotection in glaucoma. In particular, the hope raised by preclinical studies showing that drugs could have a beneficial effect on the survival of retinal ganglion cells should certainly be tempered until such an effect is confirmed by clinical trials conducted in patients with glaucoma.

[Membrane potential depolarization in the porcine ciliary epithelium evoked by nitric oxide]. / Membranpotenzial-Depolarisation im Epithel des Schweineziliarkörpers durch Stickstoffmonoxid.

BACKGROUND: The present work studies if in porcine ciliary body epithelium the intracellular signal transduction pathway nitric oxide (NO)--guanylate cyclase (GC)--3',5'-cyclic guanosinemonophosphate (cGMP) can change the membrane potential of the epithelium of the ciliary body. MATERIAL AND METHODS: Recordings of membrane potentials were done by means of intracellular microelectrodes in the presence of the NO donor Sodium Nitroprusside (SNP; 100 microM; n = 5) or the membrane permeable cGMP analogue 8-parachlorophenyl-thioguanosine-3',5' cyclic monophosphate (8-pCPT-cGMP; 100 microM; n = 5). To test whether the GC is involved in this process, recordings were repeated in both groups in presence or in absence of the GC inhibitor 1-H-(1,2,4)oxadiazole-(4,3-a)quinoxalin-1-one (ODQ; 10 microM; n = 4). RESULTS: SNP and 8-pCPT-cGMP both induced significant membrane potential depolarizations (7.7 +/- 1.8 mV and 13.1 +/- 1.3 mV, mean +/- SEM). Membrane depolarizations induced by SNP were significantly inhibited by ODQ (p < 0.01), whereas depolarizations induced by 8-pCPT-cGMP were not altered by the presence of ODQ (p > 0.2). CONCLUSIONS: Nitric oxide induces depolarizations of the membrane potential in the isolated porcine ciliary body. This process is transduced by activation of the GC. We conclude that nitric oxide might be involved in the regulation of permeability of the cellular membrane for ions in the ciliary body.

Topical ocular instillation of nitric oxide synthase inhibitors and intraocular pressure in rabbits.

PURPOSE: It has been reported that intravenous injection of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl esther (L-NAME) causes a rapid decrease of intraocular pressure (IOP) in rabbits. This study investigates the effect of topical ocular application of different NOS inhibitors on a raise of IOP induced by an acute water intake (rabbit water loading model). METHODS: Forty New Zealand (albino) male rabbits received randomly (within thirty minutes) in their right eye three 50 microliters installations of either 0.9% NaCl, 0.5% timolol maleate (beta-adrenoreceptor antagonist), 0.5% 7-nitroindazole (7-NI; NOS inhibitor), 0.5% L-NAME, or 0.5% 2-amino-5,6-dihydro-6-methyl-1,3,-thiazine (AMT; NOS inhibitor) before an oral water gavage (60 ml/kg). IOP was measured (TonoPen) before and after topical instillation (time 0), and then 15, 30, 60, 90, and 120 minutes after water intake. RESULTS: In right eyes, the area under the curve (AUC) of the IOP difference versus time (arbitrary units) was 527 +/- 284 for NaCl, 255 +/- 178 for timolol, 466 +/- 242 for 7-NI, 604 +/- 195 for L-NAME, and 394 +/- 202 for AMT. Values of AUC were only significantly lower (p < 0.05) in the timolol-treated group. In left eyes, no significant difference (p > 0.05) could be observed in values of AUC between groups. CONCLUSIONS: Under the present experimental conditions (including concentration and bioavailability of the drugs used), topical application of the NOS inhibitors 7-NI, L-NAME, and AMT does not prevent an IOP increase induced by water intake in rabbits.

Cyclic AMP and anionic currents in porcine ciliary epithelium.

INTRODUCTION: To investigate whether in the ciliary epithelium of isolated porcine ciliary body cyclic 3',5' adenosine monophosphate (cAMP) activates transmembrane anionic currents. METHODS: Changes in membrane potential induced either by the adenylcyclase activator forskolin (10 microM; n = 4) or the stable membrane permeable cAMP analog 8-bromo-adenosine 3',5'-cyclic monophosphothioate (8-br-cAMP; 30 microM; n = 4) were measured with intracellular microelectrodes. The effect of the drugs were assessed in the absence or in the presence of the non-selective anionic channel/transporter inhibitor diisothiocyanatostilbene-2,2' disulfonic acid (DIDS; 1 mM; n = 4). RESULTS: Significant (p < 0.001) membrane potential depolarization were induced by both forskolin (11.8 +/- 0.3 mV) or 8-br-cAMP (9.3 +/- 0.4 mV). In the presence of DIDS, a significant (p < 0.001) inhibition of the depolarization evoked by forskolin (0.9 +/- 1.1 mV) and 8-bromo-cAMP (0.7 +/- 0.2 mV) was observed. CONCLUSIONS: In the ciliary epithelium of isolated porcine ciliary body cAMP induces membrane potential depolarization through a process that could involve anionic channels.

PGE(2), Ca(2+), and cAMP mediate ATP activation of Cl(-) channels in pigmented ciliary epithelial cells.

Purines regulate intraocular pressure. Adenosine activates Cl(-) channels of nonpigmented ciliary epithelial cells facing the aqueous humor, enhancing secretion. Tamoxifen and ATP synergistically activate Cl(-) channels of pigmented ciliary epithelial (PE) cells facing the stroma, potentially reducing net secretion. The actions of nucleotides alone on Cl(-) channel activity of bovine PE cells were studied by electronic cell sorting, patch clamping, and luciferin/luciferase ATP assay. Cl(-) channels were activated by ATP > UTP, ADP, and UDP, but not by 2-methylthio-ATP, all at 100 microM. UTP triggered ATP release. The second messengers Ca(2+), prostaglandin (PG)E(2), and cAMP activated Cl(-) channels without enhancing effects of 100 microM ATP. Buffering intracellular Ca(2+) activity with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'- tetraacetic acid or blocking PGE(2) formation with indomethacin inhibited ATP-triggered channel activation. The Rp stereoisomer of 8-bromoadenosine 3',5'-cyclic monophosphothioate inhibited protein kinase A activity but mimicked 8-bromoadenosine 3',5'-cyclic monophosphate. We conclude that nucleotides can act at >1 P2Y receptor to trigger a sequential cascade involving Ca(2+), PGE(2), and cAMP. cAMP acts directly on Cl(-) channels of PE cells, increasing stromal release and potentially reducing net aqueous humor formation and intraocular pressure.

Common actions of adenosine receptor agonists in modulating human trabecular meshwork cell transport.

A(1) adenosine receptors (ARs) reduce, and A(2)ARs increase intraocular pressure, partly by differentially altering resistance to aqueous humor outflow. It is unknown whether the opposing effects of A(1)AR and A(2)AR agonists are mediated at different outflow-pathway cell targets or by opposing actions on a single cell target. We tested whether a major outflow-pathway cell, the trabecular meshwork (TM) cell might constitute the primary AR-agonist target and respond differentially to A(1), A(2A) and A(3)AR agonists. Receptor activation in human TM cells was identified by applying subtype-selective AR agonists: CPA and ADAC for A(1)ARs, CGS 21680 and DPMA for A(2A)ARs, and Cl-IB-MECA and IB-MECA for A(3)ARs. Stimulation of A(1), A(2A) and A(3)ARs elevated Ca(2+), measured with fura-2. Whole-cell patch clamping indicated that AR agonists activated ion channels non-uniformly, possibly reflecting variability in magnitude of agonist-triggered second-messenger responses. A(1), A(2A) and A(3)AR agonists all reduced volume, determined by calcein cell imaging. The endogenous source of adenosine delivery to the outflow pathway could be the TM cells since these cells were stimulated to release ATP by hypotonic perfusion. We conclude that: (1) TM cells express functional A(1), A(2A) and A(3)ARs; and (2) the reported differential effects of AR agonists on aqueous humor outflow are not mediated by differential actions on TM-cell Ca(2+) and volume, but likely by actions on separate cell targets.

Pupillary examination with infrared consumer videocamera.

BACKGROUND: Pupillary observation in the dark is always a problem in a general ophthalmological practice or an outpatient clinic without specialized equipment. We present two methods for observation of the pupils in darkness: 1) illumination of the pupils with the skiascope as a routine examination and 2) infrared observation of the pupils with a consumer digital video camera. METHODS: (1) Pupillary reactions are observed with the skiascope/retinoscope, the observation beam of the device focused to infinity and documented with a video camera. (2) Infrared observation of the pupils was performed with a digital consumer video camera, allowing observation of the pupillary reaction in darkness. After recording, video sequences of interest were transferred to a personal computer and the still images of interest extracted. RESULTS: In everyday clinical routine, observation of the pupillary reaction with the skiascope/retinoscope proves as a reliable tool with a large bandwidth of illumination and a high contrast between pupil and surrounding area. The infrared video camera allows an excellent visualization of the pupillary reflex in darkness. The transfer of the video sequences to a personal computer proved to be simple and single images can easily be chosen. CONCLUSION: Observation of the pupillary reflex with the skiascope proved a useful tool that is available in practically every ophthalmological office. Use of the infrared digital consumer video camera (available at low prices) is a highly sophisticated tool for observation and documentation of pupillary reflex in darkness.