Necl-1/CADM3 regulates cone synapse formation in the mouse retina.

In vertebrates, retinal neural circuitry for visual perception is organized in specific layers. The outer plexiform layer is the first synaptic region in the visual pathway, where photoreceptor synaptic terminals connect with bipolar and horizontal cell processes. However, molecular mechanisms underlying cone synapse formation to mediate OFF pathways remain unknown. This study reveals that Necl-1/CADM3 is localized at S- and S/M-opsin-containing cones and dendrites of type 4 OFF cone bipolar cells (CBCs). In Necl-1-/- mouse retina, synapses between cones and type 4 OFF CBCs were dislocated, horizontal cell distribution became abnormal, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors were dislocated. Necl-1-/- mice exhibited aberrant short-wavelength-light-elicited signal transmission from cones to OFF CBCs, which was rescued by AMPA receptor potentiator. Additionally, Necl-1-/- mice showed impaired optokinetic responses. These findings suggest that Necl-1 regulates cone synapse formation to mediate OFF cone pathways elicited by short-wavelength light in mouse retina.

Comparison of the 1-year surgical outcomes of ab interno trabeculotomy using three types of microhooks.

PURPOSE: We compared the 1-year surgical outcomes of microhook ab interno trabeculotomy (µLOT) using three types of microhooks. METHODS: We retrospectively analyzed 81 eyes that underwent µLOT, in which three microhooks, the Sinskey hook, Tanito Micro-Hook-trabeculotomy-device (TMH), and Matsushita ed. TMH, were used. We collected the data from the medical records. We analyzed the success rates and risk factors. Failure was defined as the need for additional surgery for IOP reduction, loss of light perception, and IOP ≧22 mmHg and IOP reduction <20% (definition 1), IOP ≧17 mmHg and IOP reduction <20% (definition 2), IOP ≧15 mmHg and IOP reduction <25% (definition 3), or IOP ≧12 mmHg and IOP reduction <30% (definition 4) at two consecutive follow-up visits. RESULTS: Twenty-six eyes underwent µLOT using the Sinskey microhook (group S), 21 eyes using the TMH (group T), and 34 eyes using the Matsushita ed. TMH (group M). The mean postoperative IOP and IOP-lowering medication score decreased significantly. The respective success rates among groups S, T, and M did not differ significantly (definition 1, 65.4%, 61.9%, and 55.9%; definition 2, 42.3%, 47.6%, and 32.3%; definition 3, 15.4%, 28.6%, and 23.5%; definition 4, 0%, 9.5%, and 2.9%). In group S, the hyphema-related IOP spikes decreased within 2 weeks postoperatively, and in group M, the non-hyphema-related IOP spikes decreased significantly. CONCLUSION: The 1-year surgical outcomes and complications after µLOT did not differ significantly among the three microhooks. The differences in the microhook tips might be associated with postoperative transient IOP spikes.

Deep-learning approach to detect childhood glaucoma based on periocular photograph.

Childhood glaucoma is one of the major causes of blindness in children, however, its diagnosis is of great challenge. The study aimed to demonstrate and evaluate the performance of a deep-learning (DL) model for detecting childhood glaucoma based on periocular photographs. Primary gaze photographs of children diagnosed with glaucoma with appearance features (corneal opacity, corneal enlargement, and/or globe enlargement) were retrospectively collected from the database of a single referral center. DL framework with the RepVGG architecture was used to automatically recognize childhood glaucoma from photographs. The average receiver operating characteristic curve (AUC) of fivefold cross-validation was 0.91. When the fivefold result was assembled, the DL model achieved an AUC of 0.95 with a sensitivity of 0.85 and specificity of 0.94. The DL model showed comparable accuracy to the pediatric ophthalmologists and glaucoma specialists in diagnosing childhood glaucoma (0.90 vs 0.81, p = 0.22, chi-square test), outperforming the average of human examiners in the detection rate of childhood glaucoma in cases without corneal opacity (72% vs. 34%, p = 0.038, chi-square test), with a bilateral corneal enlargement (100% vs. 67%, p = 0.03), and without skin lesions (87% vs. 64%, p = 0.02). Hence, this DL model is a promising tool for diagnosing missed childhood glaucoma cases.

Intereye comparison of visual field progression in eyes with open-angle glaucoma.

PURPOSE: To investigate the intereye correlations between and differences in the rates of visual field (VF) progression in eyes with bilateral open-angle glaucoma. STUDY DESIGN: Retrospective, longitudinal, observational study. METHODS: Patients with bilateral open-angle glaucoma with 8 or more reliable 30 - 2 standard automated perimetry tests over a period of more than 2 years were enrolled. The rate of change of the MD (MD slope) was used as the indicator for the rates of VF progression. Descriptive statistics of the absolute intereye difference in the MD slope values were computed. Factors associated with a large intereye difference (> 0.42 dB/year) were explored. RESULTS: One hundred eighty-eight eyes from 94 patients (56 women) were enrolled. A significant intereye correlation of the rates of visual field progression (P = .002) was found. The mean ± standard deviation and median intereye differences of the MD slope values were 0.29 ± 0.31 and 0.18 dB/year (range: 0-1.41), respectively. The 5th, 10th, 25th, 75th, 90th, and 95th percentiles of intereye differences were 0.01, 0.02, 0.08, 0.42, 0.72, and 0.91 dB/year, respectively. Older age and slower progression were significantly associated with large intereye difference. CONCLUSION: A significant intereye correlation in the rate of VF progression was found in eyes with bilateral open-angle glaucoma. We showed the distributions and associated factors of intereye differences in VF progression. These data may be used for improving the estimation of rates of VF progression.

Long-term course with iris changes after trabeculectomy for uveitic glaucoma associated with iris mammillation: a case report.

BACKGROUND: Iris mammillation is a rare disease characterized by the distribution of multiple nodules on the iris surface. The course of uveitic glaucoma with iris mammillation has never been reported. CASE PRESENTATION: A 56-year-old woman, who presented with unilateral decreased vision, visited our hospital for treatment of uveitic glaucoma in the right eye. Multiple nodules were scattered over the iris surface in that eye. This case was diagnosed as iris mammillation on clinical findings. After excluding malignant tumors such as melanoma, trabeculectomy was performed. The resected iris had no pathologically malignant findings. The iris nodules evolved to a sand-like appearance, and the intraocular pressure remained stable without recurrent inflammation 7 years after trabeculectomy. CONCLUSIONS: In a case of unilateral uveitic glaucoma with iris mammillation, filtration surgery was performed after excluding the presence of a malignancy, and the long-term postoperative course has been stable.

Barium-induced toxic anterior segment syndrome.

Toxic anterior segment syndrome (TASS) is a rapid-onset inflammation of the eye following uneventful ocular surgery. We report a case of TASS following Baerveldt glaucoma implant (BGI) surgery. Inductively coupled plasma-mass spectrometry (ICP-MS) identified barium in the eye and in the eluate from the bleb of the BGI. We attribute TASS in our patient to the dissolution of barium from the BGI and its entry into the eye, where it causes severe inflammation.

Case Report: Gonio-endoscopy: a novel approach to minimally invasive glaucoma surgery in a glaucomatous eye.

Background: The gonio-endoscope is a novel device for use during minimally invasive glaucoma surgery (MIGS) to treat glaucomatous eyes with cloudy cornea. The MIGS procedure requires a surgical gonioprism lens for direct visualization of the angle, intraoperative manipulation of the surgical microscope and the patient's head position, and the patient's eye without a cloudy cornea. In cases with cloudy corneas or limitation of neck movement, MIGS cannot be safely performed. Gonio-endoscopy facilitates clear visualization of the trabecular meshwork (TM) to perform MIGS safely and easily even in a patient with corneal opacities or limitation of neck movement with no additional MIGS procedures. We report the first case in which we performed the newly developed a 10,000-pixel high-resolution 23-gauge gonio-endoscopic operation. Case presentation: The patient was a 58-year-old man with Down syndrome who had secondary glaucoma bilaterally after cataract surgery and long-time use of a steroid for atopic dermatitis and allergic conjunctivitis. His left eye had a cloudy cornea after penetrating keratoplasty for keratoconus with severe corneal residual scarring after prior resolved corneal hydrops. When the intraocular pressure (IOP) in his left eye increased to 41 mmHg despite the maximum use of anti-glaucoma eyedrops, he was referred to our hospital. Anterior-segment optical coherence tomography showed an open angle. We developed a new gonio-endoscope (MACHIDA Endoscope Co., Ltd., Chiba, Japan and NIPRO CORPORATION, Osaka, Japan), the probe of which is bent appropriately to aid visualization of and access to the TM. After obtaining clinical approval from the government and our institution, we could safely perform a high-resolution 23-gauge gonio-endoscopy-assisted microhook ab interno trabeculotomy (µLOT). The IOP decreased to 10 mmHg and the visual acuity has been preserved with no major complications for 1 year postoperatively. Conclusion: This new technique of clear gonio-visualization using a gonio-endoscope might be helpful for a safe and easy µLOT in patients with cloudy corneas. This device can apply to other types of MIGS procedures and cases with pathological diagnoses of glaucoma that are difficult to treat.

Analysis of optic disc tilt angle in intrapapillary hemorrhage adjacent to peripapillary subretinal hemorrhage using swept-source optical coherence tomography.

Purpose: To report findings on the tilt angle of optic nerve heads (ONHs) that developed intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage (IHAPSH) using swept-source optical coherence tomography (SS-OCT). Observations: Five consecutive patients who presented with IHAPSH were reviewed retrospectively. We reviewed five consecutive eyes from the five patients, analyzed the optic tilt angle obtained from SS-OCT B-scans, and compared the results and other clinical characteristics. All patients had larger optic disc tilt angles in the eyes with IHAPSH than in the contralateral, unaffected eye. The mean ratio of the tilt angle in the eyes with IHAPSH to that in the contralateral eye was 1.37 (95% confidence interval 1.15-1.58). Conclusions and Importance: The ONH of IHAPSH was evaluated quantitatively with SS-OCT for the first time in this study. Larger angle tilted discs in IHAPSH-affected eyes are anatomically and histologically more vulnerable and may explain why IHAPSH develops monocularly.

Early Three-Dimensional Intrableb Structural Changes in Primary-Open Angle Glaucoma and Exfoliation Glaucoma After Ex-PRESS Surgery.

PURPOSE: To compare early-stage intrableb structural changes after Ex-PRESS surgery using anterior-segment optical coherence tomography between primary open-angle glaucoma (POAG) and exfoliation glaucoma (XFG). METHODS: Twenty-five POAG eyes and 15 XFG eyes that underwent Ex-PRESS surgery were evaluated. Intrableb images were classified into four categories based on previously reported scattering intensity: high-, medium-, and low-scattering walls and fluid-filled spaces. Bleb measurements were evaluated in both groups throughout 6 postoperative months. The 3-year surgical success was defined by the criteria intraocular pressure (IOP) < 18 mmHg and IOP < 15 mmHg with or without medications. RESULTS: The fluid-filled space volume at 3 and 6 months (P = 0.005 and P = 0.022, respectively) and the volume ratio of the low-scattering wall to the bleb wall (P = 0.028) at 6 months were significantly smaller in XFG than POAG postoperatively. The volume ratio of the high-scattering wall to the bleb wall was correlated positively (P = 0.007) with the IOP, and that of the low-scattering wall to the bleb wall was correlated negatively (P = 0.002) with the IOP in XFG. The 3-year surgical success rates for both criteria were significantly lower in XFG than POAG. CONCLUSIONS: Fluid-filled spaces were smaller in XFG than in POAG after Ex-PRESS surgery. The proportion of the high-scattering wall tended to increase and the low-scattering wall tended to decrease in XFG eyes with high IOP. Early-stage intrableb structural changes differed between POAG and XFG and may affect the prognosis. TRANSLATIONAL RELEVANCE: Our cutting-edge observation of intrableb fibrosis can be an important predictor of the surgical outcome.

Evaluating Visual Field Progression in Advanced Glaucoma Using Trend Analysis of Targeted Mean Total Deviation.

PURPOSE: Trend analysis of visual field (VF) global indices may underestimate the rate of progression in severe glaucoma because of the influence of test points without detectable sensitivity. To test this hypothesis, we compared the rates of change of VF global indices with and without exclusion of undetectable points at various disease stages. MATERIALS AND METHODS: Six hundred and forty-eight eyes of 366 glaucoma patients with 8 or more reliable 30-2 standard automated perimetry over more than 2 years were enrolled. We calculated targeted mean total deviation (TMTD) by averaging total deviation except points which were consistently undetectable in 3 baseline tests. Eyes were classified as early (≥-6 dB), moderate (-6 dB to -12 dB), advanced (-12 dB to -20 dB), and severe (<-20 dB) based on baseline mean deviation (MD). The rates of change of MD and TMTD in each stage were statistically compared. RESULTS: Mean age±SD at baseline was 56.9±11.9 years. The MD slope (-0.34 dB/y) in severe glaucoma was significantly slower than TMTD slope (-0.42 dB/y, P=0.028) and was slower than MD slopes in the other stages. Difference between MD slopes and TMTD slopes was most prominent in eyes with MD values less than -25 dB (P=0.002). CONCLUSIONS: Undetectable locations in eyes with severe glaucoma may underestimate the rates of VF progression. Trend analysis of TMTD rather than global indices offers a practical and simple approach for alleviating underestimation of VF progression in severe glaucoma.

Case Report: Getting a Peek at the Angle of a Patient with Severe Keratoconus.

Visualization of the iridocorneal angle, which contains the aqueous humor circulatory system and controls intraocular pressure, is important for diagnosing and managing glaucoma; however, the presence of keratoconus, keratoglobus, or severe myopia may enable direct angle visualization without gonioscopy contact lenses or applying a coupling gel. We present the first report of a case in which the iridocorneal angle was viewed directly in an eye with keratoconus using the RetCam without applying gel to the cornea. This method overcame the inability to view the angle directly in a normal eye because of the total internal reflection.

Intraocular Endoscopy Resolved Tube Occlusion of an Ahmed Glaucoma Valve.

We report a case in which intraocular endoscopy clarified the cause of Ahmed glaucoma valve (AGV) failure with a cloudy cornea. A 42-year-old patient with glaucoma underwent AGV implant surgery to treat secondary glaucoma due to chronic iridocyclitis in his left eye. After AGV, he developed bullous keratopathy (BK) in that eye. After Descemet stripping automated endothelial keratoplasty (DSAEK) was performed to treat BK, the intraocular pressure (IOP) increased and early failure of the DSAEK resulted again in a cloudy cornea. We could not precisely detect any cause of AGV failure with ordinary imaging instrumentation. An intraocular endoscope was used to determine that cause, and we found that the fibrous tissue occluded the tube of the AGV. The IOP decreased soon after the tissue was removed. We conclude that intraocular endoscopy was useful for diagnosing AGV failure with BK.

Prognostic factors for successful Baerveldt glaucoma implant surgery for refractory glaucoma after multiple surgeries.

PURPOSE: To determine the prognostic factors for success 3 years after Baerveldt glaucoma implant (BGI) surgery. STUDY DESIGN: Single-center retrospective clinical study. METHODS: We analyzed 27 eyes (24 patients) treated with BGI surgery between 2012 and 2016 at Osaka University Hospital. Patients were followed for a minimum of 3 years postoperatively. We analyzed the success rates and risk factors. Failure was defined as the need for additional surgery for IOP reduction, loss of light perception, and intraocular pressure (IOP) ≧22 mmHg (definition 1) or ≧17 mmHg (definition 2) at two consecutive follow-up visits. RESULTS: The mean number of previous eye surgeries was 4.1 ± 3.3. The success rates were 81.5% and 77.8%, respectively, 1 year and 3 years after surgery based on definition 1 and 51.9% and 48.2%, respectively, based on definition 2. The early and late surgical complication rates, respectively, were 29.6% and 22.2%. An IOP 2 months after BGI surgery of ≧17 mmHg and the number of previous eye surgeries were significant risk factors for failure based on definition 2. CONCLUSION: The long-term results and complication rates after BGI surgery for refractory glaucoma in our hospital were similar to previous reports, and the IOP 2 months after BGI surgery and the number of previous eye surgeries were associated with the prognosis.

Efficacy and safety of 5-fluorouracil in infrared monitor guided bleb revision.

PURPOSE: Infrared monitor-guided bleb revision (IRGBR), an alternative needling system, visualizes anterior-segment tissues around the bleb not visible during needle revision after trabeculectomy. This study determined the safety and efficiency of 5-fluorouracil (5-FU) as an adjunctive anti-metabolite in IRGBR. METHODS: We retrospectively analyzed 43 consecutive eyes (40 patients; 14 eyes, primary open-angle; 29 eyes, secondary glaucoma) treated with IRGBR for failing filtering blebs. The patients were divided into two groups. The first one had IRGBR without adjunctive 5-FU subconjunctival injection, and the second one had IRGBR with 5-FU. We performed Kaplan-Meier survival analysis using log-rank tests after 2 years of follow-up and Cox proportional hazards regression model to analyze the dependence of the survival time on predictor variables. Two failure criteria were defined as the need for additional surgery for intraocular pressure (IOP) reduction and the IOP at two consecutive follow-up visits based on definition 1, IOP ≧22 mmHg and definition 2, IOP ≧17 mmHg. RESULTS: Thirty eyes (29 cases) underwent IRGBR with subconjunctival 5-FU injection (group A in the second term) and 13 eyes (11 cases) without 5-FU (group B in the first term). The success rates 24 months after IRGBR were 73.3 and 23.1%, respectively, in groups A and B based on the definition 1 failure and 56.7 and 7.7% based on the definition 2 failure. Complications included transient bleb leaks (group A, 3 eyes; group B, none) and choroidal detachment (group A, 1 eye; group B, none). No use of 5-FU and IOPs ≧10 mmHg 1 week after IRGBR were significant risk factors. CONCLUSIONS: Adjunctive 5-FU in IRGBR achieved a better success rate for failing trabeculectomy blebs.

Complete Visual Recovery From Severe Outer Retinitis After Tonsillitis.

BACKGROUND: To report a case of severe acute bilateral outer retinitis after tonsillitis and rapid morphologic and functional recovery after steroid treatment. METHODS: Observational case report. RESULTS: A 26-year-old woman with acute bilateral blurred vision that developed after tonsillitis underwent spectral-domain optical coherence tomography (SD-OCT) that showed photoreceptor outer segment damage. Full-field electroretinography (ERG) and multifocal ERG were nonrecordable. The patient had a remarkable anatomic and functional recovery in response to steroid treatment; however, partial damage remained around the macula on SD-OCT, and an adaptive optics imaging system showed damaged cone photoreceptors. CONCLUSIONS: Prednisolone is an effective treatment for a disease that is believed to be due to suspicious involvement of the autoimmune system. Even severe outer retinitis can recover completely with rapid diagnosis and treatment.

Development of an Infrared Monitor-Guided Bleb Revision Procedure.

The needle revision procedure to address failing filtering blebs is a blind technique that might easily damage the scleral flap, conjunctiva, and choroid. We propose a new surgical procedure, infrared monitor-guided bleb revision, to perform bleb revision minimally invasively and effectively, and demonstrate the procedure in a patient. We developed the guided procedure with the infrared monitor to observe the bleb interior with greater contrast. Under the monitor, we dissect the hard fibrotic tissue with a bleb knife and, if necessary, remove adhesions using a needle and vitreous forceps. Finally, 5-fluorouracil is injected into the subconjunctiva. We have performed bleb revisions safely with clear visualization of the scleral flap using an infrared light. In the current case, the patient had good intraocular pressure control for about 1 year. The new infrared monitor-guided bleb revision procedure facilitates successful bleb revisions without damage to the underlying structures.

Assessment of a self-assembling peptide gel, SPG-178, in providing a clear operative field for trabeculectomy surgery for glaucoma in an animal model.

The presence of blood during ophthalmic surgery is problematic, as it can obstruct a surgeon's view of the operative field. This is particularly true when performing trabeculectomy surgery to enhance ocular fluid outflow and reduce intraocular pressure as a treatment for glaucoma, one of the most common vision loss conditions worldwide. In this study, we investigated the performance of a transparent, self-assembling peptide gel (SPG-178) and its ability to maintain visibility during trabeculectomy surgery. Unlike the hyaluronic acid gel commonly used in ophthalmic surgery, SPG-178 did not permit the ingress of blood into the gel itself. Rather, it forced blood to flow peripherally to the gel. Moreover, if bleeding occurred under the SPG-178 gel, perfusion with saline was able to effectively flush the blood away along the interface between the SPG-178 and the ocular tissue (in this case scleral) to clear the surgical field of view. In experimental trabeculectomy surgeries with mitomycin C used as an adjuvant, there were no differences in the postoperative recovery of intraocular pressure or bleb morphology with or without the use of SPG-178. SPG-178, therefore, when used in a gel formulation, represents a new material for use in intraocular surgery to ensure a clear operative field with likely beneficial treatment outcomes.

Association of the CAV1-CAV2 locus with normal-tension glaucoma in Chinese and Japanese.

BACKGROUND: The CAV1-CAV2 locus has been associated with primary open-angle glaucoma (POAG) and intraocular pressure. However, its association with normal-tension glaucoma (NTG) was inconclusive. Therefore, we evaluated this association in Chinese and Japanese. METHODS: Two single-nucleotide polymorphisms (SNPs, rs4236601 and rs1052990) from previous genome-wide association studies of POAG were genotyped in a total of 2220 study subjects: a Hong Kong Chinese cohort of 537 NTG patients and 490 controls, a Shantou Chinese cohort of 102 NTG and 731 controls and an Osaka Japanese cohort of 153 NTG and 207 controls. Subgroup analysis by gender was conducted. Outcomes from different cohorts were combined using meta-analysis. RESULTS: SNP rs4236601 was significantly associated with NTG in the two Chinese cohorts (Pmeta = .0019, OR = 4.55, I2 = 0). In contrast, rs4236601 was monomorphic in the Osaka cohort. The association of rs1052990 was insignificant in a meta-analysis combining Chinese and Japanese cohorts (Pmeta = .81, OR = 1.05; I2 = 64%), and the OR tended towards opposite directions between Chinese (OR = 1.26) and Japanese (OR = 0.69). Gender-specific effects of the SNPs were not statistically significant in the logistic regression or Breslow-day tests of ORs (P > .05), although rs4236601 was significant in males (P = .0068; OR = 10.30) but not in females (P = .14; OR = 2.65) in the meta-analysis of Chinese subjects. CONCLUSIONS: In this study, we confirmed the association of rs4236601 at the CAV1-CAV2 locus with NTG in Chinese. SNP rs4236601 is monomorphic, and rs1052990 tends towards a different direction in the Japanese cohort. Further studies are warranted to verify the ethnic difference and gender-specific effects of this locus.

Association of the SIX6 locus with primary open angle glaucoma in southern Chinese and Japanese.

The purpose of the study was to evaluate the association profiles of the SIX6 locus with primary open-angle glaucoma (POAG) in southern Chinese and Japanese. In this study, we tested single marker and haplotype-based associations of 11 tagging single nucleotide polymorphisms (SNPs) covering the SIX6 locus with POAG in a Hong Kong Chinese cohort (N = 1402). A novel SNP (i.e., rs12436579) and two SNPs (i.e., rs33912345 and rs10483727) from previous genome-wide association studies were further tested in a Chinese cohort from Shantou (N = 888) and a Japanese cohort from Osaka (N = 463). Results from the three cohorts were meta-analysed using a random-effect model. We found rs12436579, which has not been previously reported, was associated with POAG in Hong Kong and Shantou Chinese (Pcombined = 4.3 × 10-5, OR = 0.72, I2 = 0). Additionally, we replicated the association of one known SNP, rs33912345 (Pcombined = 0.0061, OR = 0.69, I2 = 45%), with POAG in the Chinese cohorts but not in the Japanese cohort (P > 0.6). Another known SNP, rs10483727, was nominally associated with POAG in the two Chinese cohorts (Pcombined = 0.017, OR = 0.70, I2 = 53%). All these three SNPs were significantly associated with POAG when the three cohorts were combined in meta-analysis (Pcombined<0.005). Furthermore, two haplotypes, C-C (Pcombined = 1.13 × 10-5, OR = 1.41, I2 = 0) and A-A (Pcombined = 0.045, OR = 0.68, I2 = 70%), defined by rs33912345-rs12436579 were associated with POAG in Chinese but not in Japanese. In conclusion, this study confirmed the association between two GWAS SNPs in SIX6 (rs33912345 and rs10483727) and POAG. Also, a SNP, rs12436579, not associated with POAG before, was found to be associated with POAG in Chinese. Further studies are warranted to elucidate the role of this novel SNP in POAG.

Contribution of Bipolar Cells of Cone ON and OFF Pathways to Electroretinograms Elicited by Ultraviolet and Middle Wavelength Stimuli.

PURPOSE: To determine the contribution of the ON and OFF cone bipolar cell pathways to the electroretinograms (ERGs) elicited by ultraviolet (UV) and middle wavelength light in mice. MATERIALS AND METHODS: The experiments were performed on 8- to 10-week-old C57BL/6J mice. The ERGs elicited by single-flash and flickering UV light stimuli were compared to those elicited by green light stimuli under photopic conditions. Pharmacological agents were used to selectively block the ON and OFF pathways contributing to the ERGs. Saline was used as a control. The flicker ERGs elicited by UV light were compared to the ERGs elicited by green light after the injection of the pharmacological agents to determine the contribution of the cone ON and OFF pathways to the ERGs. RESULTS: The photopic single-flash and flicker ERGs were more sensitive to the UV light stimuli than to those elicited by green light stimuli. The flicker ERG responses elicited by both UV and green light stimuli at stimulus frequencies lower than 15-Hz decreased after L-2-amino-4-phosphobutyric acid was injected. The ERGs elicited by UV light at 30-Hz and by green light at frequencies lower than 15-Hz decreased significantly after the intravitreal injection of cis-2, 3-piperidine-dicarboxylic acid. An analysis of the ON and OFF components of the flicker ERGs showed that there might be pharmacological differences between the UV light-sensitive responses and the green light-sensitive responses. CONCLUSIONS: These results suggest that the UV light-sensitive cones connect to both the ON and OFF bipolar cells differently than that of the green light-sensitive cones.