A case of herpes zoster ophthalmicus with optic neuritis of the total length of the optic nerve in the orbital space and ischemic optic neuropathy.

Purpose: We herein report a case of optic neuritis and ischemic optic neuropathy associated with herpes zoster ophthalmicus and decreased visual acuity. Observations: A 65-year-old man with no special medical history had a headache on the right side in December 2019, and a few days later, a facial rash appeared on the same side. A dermatologist diagnosed him with herpes zoster ophthalmicus and started antiviral drug therapy. On the same day, he was referred to a local ophthalmologist and was found to have inflammatory signs in his right cornea and conjunctiva. The next day, when he visited the ophthalmologist again, he had decreased visual acuity, optic disc swelling, and fundus hemorrhaging in his right eye, so he was referred to our department. At the first visit to our department, his best-corrected visual acuity was light sense OD, 1.0 OS. His right fundus showed optic disc swelling, spotted fundus hemorrhaging, and dilation/tortuosity of the retinal vein. Fluorescein angiography showed the near absence of optic disc filling as well as delayed retinal vein perfusion in his right eye, and magnetic resonance imaging confirmed high signals in the total length of the right optic nerve in the orbital space using the short inversion-time inversion recovery method. Based on these findings, we diagnosed him with optic neuritis and ischemic optic neuropathy associated with inflammation of the orbital part caused by herpes zoster ophthalmicus. We started systemic administration of antiviral drugs (acyclovir) and oral steroid. However, after treatment, his visual acuity improved only to hand motion OD, and the fundus appearance was ultimately optic atrophy OD. Conclusion and Importance: Various complications can occur with herpes zoster ophthalmicus, however, few reports have described cases of herpes zoster ophthalmicus associated with optic neuritis and ischemic optic neuropathy. Therefore, there is no consensus concerning the ideal treatment for these conditions. By referencing cases involving issues such as orbital apex syndrome and optic neuritis caused by herpes zoster ophthalmicus, antiviral drugs and oral steroids were administered, but the prognosis of the visual acuity was poor.

A Case of Anti-BP180-type Mucous Membrane Pemphigoid with IgG and IgA Autoantibodies Showing Distinct Reactivities.

Dear Editor, Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease characterized by erosive mucosal lesions mainly on the oral and ocular mucosae (1). We report a case of oral and ocular anti-BP180-type MMP with variable IgG and IgA reactivities and underlying dementia. An 84-year-old Japanese man presented with a 4-year history of erosions in the oral cavity and on the conjunctivae, with progressive vision impairment. The medical history included benign prostatic hyperplasia, cataract, sinusitis, and dementia. Physical examination revealed erosions and white atrophic scars along the gingival mucosa and on the hard palate (Figure 1, a, b). Conjunctival inflammation and corneal scarring were also observed only on the left eye (Figure 1, c, d). No lesions were observed on the skin or on any other mucosae. A skin biopsy from the patient's oral mucosa showed lymphocytic infiltration in the superficial dermis without apparent subepithelial blister. Direct immunofluorescence showed linear depositions of IgG, IgA, and C3 at the epithelial basement membrane zone (Figure 1, e-g). Circulating IgG and IgA autoantibodies were not detected by indirect immunofluorescence of normal human skin, while circulating IgA, but not IgG, autoantibodies were bound to the epidermal side of 1M NaCl-split normal human skin at 1:10 serum dilution (Figure 1, h, i). Commercially available IgG enzyme-linked immunosorbent assays (ELISAs) of BP180 NC16a domain, BP230, and type VII collagen (MBL, Nagoya, Japan) showed negative results. IgG and IgA immunoblotting analyses of six different antigen sources, including BP180 C-terminal domain recombinant protein, were all negative. However, ELISA of full-length BP180 was slightly positive for IgG antibodies (index = 5.79; cut-off <4.64). Immunoblotting analysis of full-length BP180 was negative for both IgG and IgA antibodies (Figure 1, j, k). Immunoblotting analysis of hemidesmosome-rich fraction was negative for both IgG and IgA antibodies to integrin ß4 (Figure 1, l). Based mainly on the clinical and immunological findings, we established a diagnosis of MMP with IgG and IgA autoantibodies, likely reactive with BP180. Because the patient refused systemic treatments, we prescribed a mouth rinse sodium gualenate hydrate and eyedrops of fluorometholone and purified sodium hyaluronate, which did not improve the oral and ocular mucosal symptoms during the 8 month follow-up period (Figure 1, m, n). Both IgG and IgA autoantibodies in anti-BP180-type MMP tend to react with the C-terminal domain of BP180 (2), and IgG autoantibodies in 39.7% of MMP patients reactive with the epidermal side of split skin were reported to be positive with BP180 C-terminal domain (3). The full-length BP180 ELISA shows excellent sensitivity for diagnosing BP180-type MMP (4). The different IgG and IgA reactivities among various methods used in the present study may be attributed either to different methodologies (i.e., immunoblotting or ELISA) or to the different substrates, since BP180-type MMP targets various regions of BP180, including the NC16a domain, the C-terminal domain, and the intracytoplasmic region (5). Precise diagnosis for MMP by various immunological methods is critical, because urgent and extensive treatments are necessary for the ocular and laryngeal lesions, which may result in loss of eyesight and airway obstruction, respectively. Acknowledgments: We express our gratitude to Ms. Mako Mine and Dr. Daisuke Hayashi, Department of Dermatology, Osaka City University Graduate School of Medicine in Osaka, Japan for the HD-rich fraction immunoblotting analysis, and Dr. Yoshiaki Hirako, Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Aichi, Japan for the preparation of the HD-rich fraction sample. This work was supported by JSPS KAKENHI Grant Number JP20k08684 and the Hirosaki University Research Support System.

Racemose hemangioma complicated with macular macroaneurysm rupture.

PURPOSE: To describe a rare case of racemose hemangioma which developed spontaneous macular macroaneurysm (MA) rupture and vitreaous hemorrhage. OBSERVATIONS: A 29-year-old healthy asian female visited our hospital and a racemose hemangioma was found in the left eye. At presentation, the best corrected visual acuity (BCVA) was 30/20 in her left eye. At 9 years after the first visit, MA-like lesion was noted in the macular area. After that, vitreous and subretinal hemorrhage appeared in the left eye. The patient underwent simultaneous vitrectomy and cataract surgery, but vitreous re-hemorrhage occurred two days after the operation. To avoid re-hemorrhage, silicone oil (SO) tamponade was added in the second vitrectomy. Two years after the second operation, SO was removed and postoperative BCVA in the left eye was 20/200 without re-bleeding in the vitreous. CONCLUSIONS AND IMPORTANCE: Although retinal hemorrhages have been reported in the patients with a racemose hemangioma, in our case the macular MA rupture occurred at 9 years after the first visit. Congenital retinal arteriovenous anastomosis can show a change in vascular shape in some cases, thus it is important to observe carefully.

A Case of Cyclodialysis after Microhook Trabeculotomy Treated with Vitreous Surgery.

We report a case of cyclodialysis with decreased visual acuity after microhook trabeculotomy (mTLO) successfully treated by vitreous surgery. A 41-year-old man had been medically treated for primary open-angle glaucoma in both eyes. He was scheduled to undergo mTLO due to progression of visual field impairment and unstable intraocular pressure in his right eye. His preoperative best-corrected visual acuity (BCVA) was 0.4 OD, and the intraocular pressure was unstable, ranging from 12 to 27 mm Hg. On the day after the operation, a shallow anterior chamber developed, and a low intraocular pressure occurred. His visual acuity continued to decrease, and cyclodialysis was confirmed by ultrasonic biomicroscopy. No improvement was obtained with medical treatment, and his BCVA dropped to 0.08 OD, while his intraocular pressure remained at 2-3 mm Hg. Three months later, a second surgery was performed by combining cataract surgery with intraocular lens implantation, vitrectomy, cryopexy for the pars plana of the ciliary body, and 20% SF6 gas tamponade. Two weeks after the reoperation, the intraocular pressure had been normalized to 12 mm Hg, and the BCVA had returned to 0.3. We successfully treated cyclodialysis as a complication after mTLO by vitreous surgery that led to the recovery of the visual acuity and intraocular pressure.

The protective effect of astaxanthin on the ganglion cell complex in glutamate/aspartate transporter deficient mice, a model of normal tension glaucoma, analyzed by spectral domain-optical coherence tomography.

Astaxanthin (AST), a natural marine carotenoid, possess a wide variety of biological functions. In particular, as a strong antioxidant, AST effectively scavenges oxygen free radicals and reduces oxidative stress. In addition, recent in vitro studies have suggested that AST attenuates glutamate-induced apoptosis and cytotoxicity. The glutamate/aspartate transporter (GLAST) deficient (GLAST-/-) mouse is a mouse model of normal tension glaucoma (NTG) caused by both the glutamate neurotoxicity and oxidative stress in the retina. In the present study, we investigated the effects of AST on the ganglion cell complex, indicator of glaucomatous structural damage, using spectral domain-optical coherence tomography. As a result, AST significantly attenuated the thinning of ganglion cell complex in GLAST-/- mice in comparison to an AST-free control group. Our results suggest the possibility that AST has protective effects against glutamate neurotoxicity and oxidative stress in the retina. At present, the only treatment for NTG that is available in the clinical setting is to reduce the IOP as much as possible. Thus, our results suggest that AST supplementation may be effective for some types of NTG in which glutamate neurotoxicity and oxidative stress are involved.

Proliferative diabetic retinopathy without preoperative pan-retinal photocoagulation is associated with higher levels of intravitreal IL-6 and postoperative inflammation.

PURPOSE: Intravitreal cytokine levels and differences in the severity of postoperative inflammation in patients with proliferative diabetic retinopathy (PDR) were compared between subjects treated with pan-retinal photocoagulation (PRP) prior to undergoing vitreous surgery and those treated similarly during the surgery. SUBJECTS AND METHODS: We examined 130 eyes of PDR patients who underwent an initial surgical procedure at Hirosaki University Hospital. A total of 67 out of the 130 eyes were treated with PRP prior to surgery (preoperative group), while 63 underwent similar treatment during surgery (intraoperative group). Vitreous fluid was collected at the start of the vitreous surgical procedure. Following vitrectomy, intraoperative PRP was completed during the surgery in the intraoperative group. This procedure was added to the peripheral part as needed in the preoperative group. The results for the levels of 27 cytokines, including vascular endothelial growth factor (VEGF), were measured using multiplex assays and compared between the groups. For determining postoperative inflammation, eyes in which fibrin was observed for 3 days or longer in the anterior chamber or vitreous cavity were considered to have fibrin deposition. The rate of fibrin deposition was compared between these groups. RESULTS: Among the vitreous cytokines examined, there was no significant difference in the VEGF levels between the groups (p = 0.70). In contrast, the IL-6 level was significantly higher in the intraoperative group (2813.2 ± 6022.2 vs. 1248.5 ± 1442.2 pg/ml, p = 0.048). Furthermore, the fibrin deposition rate was significantly higher in the intraoperative (44.4%) versus the preoperative group (14.9%) (p = 0.0002). CONCLUSION: Severe postoperative inflammation was frequently seen in patients who did not undergo preoperative PRP, which may have been due to the performance of the procedure during the surgery. Moreover, these results may also be associated with a higher level of intravitreal IL-6.

The qualitative assessment of optical coherence tomography and the central retinal sensitivity in patients with retinitis pigmentosa.

PURPOSE: To analyze the relationships between qualitative and quantitative parameters of spectral-domain optical coherence tomography (SD-OCT) and the central retinal sensitivity in patients with retinitis pigmentosa (RP). MATERIALS AND METHODS: Ninety-three eyes of 93 patients were finally enrolled, with a median age (quartile) of 58 (24.5) years. We assessed the patients using SD-OCT and the 10-2 program of a Humphry Field Analyzer (HFA). As a qualitative parameter, two graders independently classified the patients' SD-OCT images into five severity grades (grades 1-5) based on the severity of damage to the photoreceptor inner and outer segments (IS/OS) layer. As quantitative parameters, we measured the IS-ellipsoid zone (IS-EZ) width, IS/OS thickness, outer nuclear layer (ONL) thickness, central macular thickness (CMT, 1 and 3 mm) and macular cube (6 × 6 mm) volume and thickness. The central retinal sensitivity was defined by the best-corrected visual acuity (BCVA; logMAR), average sensitivities of the central 4 (foveal sensitivity [FS]) and 12 (macular sensitivity [MS]) points of the HFA 10-2 program and the mean deviation (MD) of the 10-2 program. Spearman's correlation was used to assess the association between both qualitative and quantitative parameters and variables of the central retinal sensitivity. In addition, we performed a multiple regression analysis using these parameters to identify the parameters most strongly influencing the central retinal sensitivity. RESULTS: The IS/OS severity grade was significantly correlated with the BCVA (ρ = 0.741, P < 0.001), FS (ρ = -0.844, P < 0.001), MS (ρ = -0.820, P < 0.001) and MD (ρ = -0.681, P < 0.001) and showed stronger correlations to them than any other quantitative parameters including the IS-EZ width, IS/OS thickness, ONL thickness, CMTs and macular cube volume/thickness. Furthermore, a step-wise multiple regression analysis indicated that the IS/OS severity grade was more strongly associated with the BCVA (ß = 0.659, P < 0.001), FS (ß = -0.820, P < 0.001), MS (ß = -0.820, P < 0.001) and MD (ß = -0.674, P < 0.001) than any other quantitative parameters. The intraclass correlation coefficient between two graders indicated substantial correlation (κ = 0.70). DISCUSSION: The qualitative grading of OCT based on the severity of the IS/OS layer was simple and strongly correlated with the central retinal sensitivity in patients with RP. It may be useful to assess the central visual function in patients with RP, although there is some variation in severity within the same severity grade.

Modified Intraocular Lens Intrascleral Fixation Technique Using Two Vitrectomy Ports as Lens Haptic Fixation Sites.

INTRODUCTION: We developed a new technique that uses two of the vitrectomy ports as intraocular lens (IOL) haptic fixation sites and compared that with a conventional T-fixation method. METHODS: A total of 33 eyes were retrospectively divided into the port-fixation (n=21) and conventional (n=12) groups. For the port-fixation group, supranasal and inferotemporal trocars (25-gauge) were placed in the center of a T-shaped lamellar scleral incision 2 mm from the corneal limbus and a supratemporal trocar at 3.5 mm. Following a vitrectomy, along with lens or IOL extraction as needed, the infusion cannula was changed from an inferotemporal to supratemporal trocar. The first IOL haptic and trocar were then simultaneously withdrawn from the eye by grasping with vitreoretinal forceps, with the same performed for the second IOL haptic and trocar, after which the infusion cannula was removed. In the conventional group, 2 T-shaped scleral incisions and three trocars were separately placed. RESULTS: Postoperatively, transient ocular hypotension and hypertension were observed in a few eyes in both groups. At 6 months after surgery, astigmatism was 1.71±1.13 D in the port-fixation group and 2.21±1.78 D in the conventional group (p=0.40, t-test). CONCLUSION: This new technique may be effective because of the lower number of scleral wounds.

A spectral-domain optical coherence tomographic analysis of Rdh5-/- mice retina.

PURPOSE: To investigate the longitudinal findings of spectral-domain optical coherence tomography (SD-OCT) in relation to the morphologic features in Rdh5 knockout (Rdh5-/-) mice. MATERIALS AND METHODS: The mouse retina was segmented into four layers; the inner retinal (A), outer plexiform and outer nuclear (B), rod/cone (C), and retinal pigment epithelium (RPE)/choroid (D) layers. The thickness of each retinal layer of Rdh5-/- mice was longitudinally and quantitatively measured at six time points from postnatal months (PM) 1 to PM6 using SD-OCT. Age-matched C57BL/6J mice were employed as wild-type controls. The data were statistically compared using Student's t-test. The fundus appearance was assessed, histologic and ultrastructural examinations were performed in both groups. RESULTS: Layers A and B were significantly thinner in the Rdh5-/- mice than in the wild-type C57BL/6J mice during the observation periods. Layers C and D became thinner in the Rdh5-/- mice than in the wild-type mice after PM6. Although no abnormalities corresponding to whitish fundus dots were detected by SD-OCT or histologic examinations, the intracellular accumulation of low-density vacuoles was noted in the RPE of the Rdh5-/- mice by electron microscopy. The photoreceptor nuclei appeared less dense in the Rdh5-/- mice than in the wild-type mice. DISCUSSION: The results from the present study suggest that although it is difficult to detect qualitative abnormalities, SD-OCT can detect quantitative changes in photoreceptors even in the early stage of retinal degeneration induced by the Rdh5 gene mutation in mice.

Intraoperative choroidal detachment occurring in a case of perforating ocular injury.

PURPOSE: To describe an intraoperative choroidal detachment due to balanced salt solution (BSS) leakage through the exit wound in a case with perforating ocular injury. OBSERVATIONS: The patient was a 22-year-old man who suffered from a left eye injury caused by a piece of wire during work. Vitrectomy was started after closure of the scleral wound, but surgical procedure could not be continued, as BSS leakage occurred into the subretinal and supra-choroidal spaces, resulting in a narrowed vitreous cavity, as we were slow to recognize the presence of the perforating ocular injury in this patient. Fluid-air exchange and air-silicone oil exchange in the vitreous cavity were performed to finish the initial surgery. Three weeks later, the reoperation was performed to remove silicone oil and insert an intraocular lens into the bag. Presently, 1 year 5 months following the second surgery, corrected visual acuity is 20/50. CONCLUSIONS AND IMPORTANCE: Our findings indicate that BSS can leak through the exit wound into the subretinal and supra-choroidal spaces intraoperatively in a case of perforating ocular injury.

Serum anti-recoverin antibodies is found in elderly patients with retinitis pigmentosa and cancer.

PURPOSE: To screen for anti-recoverin antibodies in elderly patients with retinitis pigmentosa (RP) with or without cancer and cross-sectionally characterize the seropositive patients clinically. METHODS: Serum from 75 RP patients who had been tested for mutations in a panel of 83 RP genes and 73 normal controls, all aged 50-80 years, were screened for anti-recoverin antibodies by Western blot using recombinant recoverin, retinal lysate from a marmoset and commercial anti-recoverin antibodies as a control. RESULTS: Three RP patients with typical pigmentary degeneration of the 75 (4.0%) were seropositive for anti-recoverin antibody. Pathogenic mutations were identified in two seropositive RP patients. All three patients had visual impairment since childhood and were diagnosed as RP by the age of 30. The severity of the retinopathy varied greatly among these three patients, ranging in visual acuity from light perception OU to 20/30 OU. Retinitis pigmentosa (RP) patients with a history of cancer were more likely to have anti-recoverin antibodies (3/14; 21.4%) than those without (0/61; 0%; p = 0.005, Fischer exact test). All 73 healthy controls with no history of cancer were also seronegative. CONCLUSION: Our results show that serum anti-recoverin antibodies can be detected in typical RP patients with identified pathogenic mutations and that a history of cancer may increase the risk of developing anti-recoverin antibodies.

Excess Glutamate May Cause Dilation of Retinal Blood Vessels in Glutamate/Aspartate Transporter-Deficient Mice.

PURPOSE: To investigate the longitudinal findings of fundus features and spectral-domain optical coherence tomography (SD-OCT) to characterize the morphologic features in a mouse model of defective glutamate/aspartate transporter (GLAST-/- mice). MATERIALS AND METHODS: The fundus findings and SD-OCT images were longitudinally recorded at five time points from postnatal (P) 22 to P156 in GLAST-/- mice. As a control wild type, age-matched C57BL/6J mice were employed. The mouse retina was subdivided into five layers, and the thickness of each layer was longitudinally measured by InSight® using SD-OCT pictures. The SD-OCT findings were compared with the histologic appearances. The diameter of the retinal blood vessels was measured by the ImageJ® software program using SD-OCT images. The data were statistically compared between both age-matched mouse groups. RESULTS: The retinal blood vessels appeared more dilated in GLAST-/- mice than in wild-type mice. This tendency was statistically significant at all time points after P44 by analyses using SD-OCT images. The ganglion cell complex (GCC) and outer nuclear layer (ONL) were significantly thinner in GLAST-/- mice at all time points after P80 than in the wild-type mice. This tendency was more clearly indicated by SD-OCT than histologic sections. DISCUSSION: In the present study, we found for the first time the dilation of the retinal blood vessels and the thinning of the ONL in GLAST-/- mice, in addition to the thinning of the GCC.

Optical Coherence Tomography of Animal Models of Retinitis Pigmentosa: From Animal Studies to Clinical Applications.

PURPOSE: The aim of this study was to understand the relationship between the findings of spectral-domain optical coherence tomography (SD-OCT) of previously reported animal models of retinitis pigmentosa (RP) associated with known genetic mutations and their background structural and functional changes. METHODS: We reviewed previous publications reporting the SD-OCT findings of animal models of RP and summarized the characteristic findings of SD-OCT in nine different animal models (RCS -/- , RHO P23H, RHO S334ter, RHO -/- , Rpe65 -/- , rp12, Pde6ß -/- (rd1 and rd10), and Arr1 -/- ) of human RP. RESULTS: Despite the various abnormal structural changes found in these different animal models, progressive thinning of the outer nuclear layer (ONL) and hyperreflective change in the inner and outer segment (IS-OS) layers of the photoreceptors were commonly observed on SD-OCT. In the rapidly progressive severe photoreceptor degeneration seen in rd10 and Arr1 -/- mice, the ONL appeared hyperreflective. Electroretinography revealed various degrees of disease severity in these animal models. Discussion and Conclusion: SD-OCT is sensitive enough to detect even mild changes in the photoreceptor OS. Conversely, SD-OCT cannot qualitatively differentiate the pathologic and functional differences in the photoreceptors associated with different genetic abnormalities, with the exception of the rapid progression of severe forms of photoreceptor degeneration. These findings can be of value to understand better the clinical findings and the heterogeneous degenerative processes in patients with RP.

Phenotypic Features of Oguchi Disease and Retinitis Pigmentosa in Patients with S-Antigen Mutations: A Long-Term Follow-up Study.

PURPOSE: To present phenotypic features of 22 patients with S-antigen (SAG) mutations. DESIGN: Retrospective cohort study. PARTICIPANTS: Twenty-one Japanese patients from 16 families with a homozygous c.924delA mutation and 1 patient with a homozygous c.636delT mutation in the SAG gene. METHODS: Clinical records on symptoms; best-corrected visual acuity; and Goldmann perimetry, fundus photography, fundus autofluorescence (FAF), OCT, and electroretinography results were reviewed. MAIN OUTCOME MEASURES: Best-corrected visual acuity, Goldmann perimetry results, imaging findings, and electroretinography results. RESULTS: Ten patients had Oguchi disease and 12 had retinitis pigmentosa (RP) with mean follow-up periods of 13.8 and 10.2 years, respectively. Retinitis pigmentosa patients were older (mean age, 56.0 years) than those with Oguchi disease (mean age, 22.1 years; P < 0.001) at the initial visit. Night blindness noted in childhood was the most common initial symptom for both Oguchi disease (80.0%) and RP (91.7%) patients. Best-corrected visual acuity in the logarithm of the minimum angle of resolution (logMAR) was well preserved in Oguchi disease patients (mean, 0.02 logMAR in both eyes) but reduced in most RP patients (mean, 1.32 logMAR [right eye] and 1.35 logMAR [left eye]). Similarly, the visual field in the retinal area was preserved in Oguchi disease patients (mean, 677 mm2 right eye and 667 mm2 left eye) and reduced in RP patients (mean, 369 mm2 right eye and 294 mm2 left eye). Fundus images revealed a characteristic golden sheen with no retinal degeneration in Oguchi disease patients, excluding 2 with macular degeneration detected by FAF, OCT, or both and 1 with mild retinal degeneration confirmed by OCT and fluorescein angiography. Pigmentary retinal degeneration most evident posteriorly was observed in RP patients, accompanied by a characteristic golden sheen in 12 of 14 patients undergoing ultra-widefield fundus imaging. OCT showed disrupted macular structure, and FAF revealed variable hypofluorescence. Electroretinography identified absent rod responses in both diseases, along with relative preservation of cone responses in Oguchi disease patients. Three patients showed progressive loss of the golden sheen based on fundus images, including 1 who demonstrated RP 26 years after the initial diagnosis of Oguchi disease. CONCLUSIONS: Retinitis pigmentosa with SAG mutations often shows a characteristic golden sheen surrounding posterior pigmentary retinal degeneration. Oguchi disease can show progressive degeneration in adulthood, rarely resulting in RP.

N-Methyl-N-Nitrosourea-Induced Photoreceptor Degeneration Is Inhibited by Nicotinamide via the Blockade of Upstream Events before the Phosphorylation of Signalling Proteins.

N-methyl-N-nitrosourea (MNU), a known carcinogen, is generally used in animal models to chemically induce photoreceptor degeneration. It has been reported that nicotinamide (NAM) exerts a protective effect on MNU-induced photoreceptor degeneration. We investigated the molecular mechanisms on MNU-induced photoreceptor degeneration. Intraperitoneal MNU injection (75 mg/kg) in rats induced selective photoreceptor degeneration in 7 days. NAM administration completely inhibited photoreceptor degeneration. Photoreceptor layer abnormality was observed within 6 hours after MNU injection, whereas it was restored in the NAM-treated retina, as detected by optical coherence tomography. One day following MNU administration, phosphorylation of the cell death-associated signalling proteins c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) increased, while the apoptosis-related proteins, full-length poly(ADP-ribose) polymerase (PARP) and apoptosis-inducing factor (AIF), were depleted. These changes were not observed in the NAM-treated retinas. Cell survival signalling, such as extracellular signal-regulated kinase (ERK), Akt, and cAMP response element binding protein (CREB) phosphorylation, increased in the MNU- but not in the NAM-treated rat retinas. Increased phosphorylated ERK (p-ERK) levels were observed within 6 hours after MNU administration, suggestive of cell survival signalling activation. This did not occur in NAM-treated retinas. These results indicate that NAM regulates upstream cellular events prior to the activation of cell death-related signalling events, such as JNK and p38 phosphorylation.

The findings of optical coherence tomography of retinal degeneration in relation to the morphological and electroretinographic features in RPE65-/- mice.

PURPOSE: Mutations of the gene encoding RPE65 cause Leber congenital amaurosis (LCA) retinitis pigmentosa (RP). The optical coherence tomography (OCT) is increasingly utilized to noninvasively evaluate various types of retinal diseases, including RP. The present study was conducted to characterize the OCT findings of the RPE65-/- mice-an animal model of LCA and RP-in relation to the morphological features based on histological and electron microscopic findings as well as electroretinography (ERG) features. MATERIALS AND METHODS: RPE65-/- mice were employed as a model of retinal degeneration. C57BL/6J mice were used as a wild-type control. OCT was performed on the RPE65-/- mice from postnatal day (P) 22 to 170. The longitudinal changes in the OCT images and fundus pictures were analyzed both qualitatively and quantitatively in comparison to those of C57BL/6J mice. The OCT images were also compared to the histological and electron microscopic findings. Full field combined rod and cone ERG was performed to analyze the relationship between morphology based on OCT and the amplitudes of the a- and b-waves. RESULTS: In the RPE65-/- mice, the photoreceptor rod and cone layer appeared as a diffuse hyperreflective zone contiguous with the inner segment ellipsoid zone (IS-EZ) on OCT, even on P22, whereas the IS-EZ and interdigitation zone were clearly identified in the age-matched C57BL/6J mice. The histological analyses revealed that the regular arrangement of the photoreceptor inner and outer segments was gradually lost in the RPE65-/- mice. On electron microscopy, most of the rod outer segments were degenerated from P21 to P35, whereas outer segments became variably shorter after P49 although ultrastructure appeared to normalize. The thickness of the outer nuclear layer of RPE65-/- mice was slowly and progressively reduced in comparison to C57BL/6J mice. Although the thickness of the inner and outer segment layer of RPE65-/- mice was significantly decreased in comparison to C57BL/6J mice, the change was not progressive, at least until P170. Even at P35, the amplitudes of both a- and b-waves on ERG were severely deteriorated in comparison to those of C57BL/6J mice. Mottled depigmented spots appeared throughout the fundus in RPE65-/- mice after P72, and were detected as hyperreflective deposits under the retinal pigment epithelium on OCT. DISCUSSION: The pathological changes in the inner and outer segments layer of RPE65-/- mice were identified as diffuse hyperreflective changes on OCT. The rod outer segments showed degeneration in the early postnatal periods but became morphologically normalized in the disc structure after P49, although the sizes of the length of the rod outer segments were variable. OCT could not qualitatively differentiate the early degeneration of rods from the late variability in size of rods. Although the morphology of the photoreceptor outer segments was relatively preserved in the RPE65-/- mice, the amplitudes of ERG were severely disturbed. These structural and functional deficits may be derived from the defective supply of 11-cis-retinol to the photoreceptors.

The Spectral-Domain Optical Coherence Tomography Findings Associated with the Morphological and Electrophysiological Changes in a Rat Model of Retinal Degeneration, Rhodopsin S334ter-4 Rats.

PURPOSE: To characterize the spectral-domain optical coherence tomography (SD-OCT) findings of the rhodopsin S334ter transgenic rats (line 4) in relation to the morphologic and electroretinographic features. MATERIALS AND METHODS: Rhodopsin S334ter transgenic rats (line 4) were employed as a model of retinal degeneration. The Sprague-Dawley (SD) rats were used as a wild-type control. SD-OCT (Micron IV®; Phoenix Research Labs, Pleasanton, CA, USA) was performed on the S334ter rats (line 4) from postnatal days (P) 13-110. The longitudinal changes of the SD-OCT images were analyzed both qualitatively and quantitatively in comparison to those of SD rats. The SD-OCT images were also compared to the histological and electron microscopic findings from examination performed on P 22, 36, and 61. Full field combined rod and cone electroretinography (ERG) was performed and the relationship between the thickness of the retinal sublayers and the amplitudes of the a- and b-waves was further analyzed. RESULTS: The photoreceptor inner and outer segment layer became diffusely hyperreflective in the SD-OCT images of the S334ter rats; these findings were not observed in the SD rats. This hyperreflective change corresponded to the degenerated inner and outer segments and the accumulation of the extracellular vesicles in the interphotoreceptor matrix. Quantitatively, the retinal outer sublayer and the photoreceptor sublayer in the S334ter rats became progressively thinner in comparison to those in the SD rats; the difference was statistically significant. The amplitudes of both the a- and b-waves on ERG were severely deteriorated in the S334ter rats. DISCUSSION: The SD-OCT images in the S334ter rats noninvasively provided information regarding the pathological changes in the photoreceptors and the longitudinal changes of both qualitative and quantitative changes during retinal degeneration in the S334ter rats (line 4). The pathological features of the photoreceptor inner and outer segments can be detected on SD-OCT as diffuse hyperreflective changes in the photoreceptor layer.

Intraocular lens intracapsular fixation with unilateral loop suture for 180 degree Zinn's zonule dialysis.

We developed intraocular lens (IOL) fixation procedure that only uses one suture during Zinn's zonule dialysis portion of the combined surgery for IOL intracapsular fixation and unilateral loop suture for preserving the lens capsule. We treated 15 eyes in 15 patients which were confirmed to have almost 180° zonular dialysis during cataract surgery. After removing the lens, a scleral flap was created on the dialysis side. A straight needle for suturing was then inserted into the anterior chamber from the opposite side of the dialysis. The needle was used to attach the equatorial segment of the capsule on the dialysis side from the inside to the outside and then pull the suture thread under the scleral flap. After the thread was bound to a preceding loop of IOL, the IOL was inserted into the bag. Our procedure was found to be simple and less invasive, as our technique required no vitrectomy to be performed.

Macular edema associated with intraocular ointment after cataract surgery.

PURPOSE: To report a case with macular edema associated with uveitis, a decreased corneal endothelial cell density, and vitreous opacity caused by migrated intraocular antibiotic ointment after uneventful cataract surgery. OBSERVATIONS: A 63-year-old man underwent uneventful sutureless superior clear corneal phacoemulsification and implantation of an intraocular lens in his right eye. Eleven months later, he complained of blurred vision when he gazed downward. Three months later, uveitis, vitreous opacity, and retinal hemorrhage were noted. Optical coherence tomography and fluorescein angiography demonstrated macular edema in the right eye. A slit-lamp examination revealed many tiny oily deposits on the iris surface. One month later, a globular oily droplet was detected at the 12 o'clock position of the iridocorneal angle. Because the corneal endothelial cell density appeared to be progressively decreased, the oily droplet was removed, and the anterior chamber was irrigated with a balanced salt solution using an irrigation-aspiration cannula. After surgery, the macular edema, vitreous opacity, and retinal hemorrhage disappeared. CONCLUSIONS AND IMPORTANCE: In this case, ofloxacin ointment had presumably migrated into the anterior chamber through a corneal incision after cataract surgery. The fact that the droplet of ointment was able to be detected more than one year after the cataract surgery suggests that dispersed tiny droplets can slowly coalesce into a globular droplet and wander between the anterior and posterior chambers, thereby causing uveitis, corneal endothelial cell damage, and macular edema. The removal of the intraocular ointment resolved these complications. This is the second report of intraocular ointment causing macular edema.

Intraoperative Adjunctive Mitomycin C and Cryotherapy for Recurrent Conjunctival Papillary Sebaceous Carcinoma.

PURPOSE: To report a case of recurrent conjunctival papillary sebaceous carcinoma that was successfully treated by a combination of surgical resection, intraoperative topical mitomycin C application, and cryotherapy. OBSERVATIONS: A woman in her 80s developed a yellowish papillary tumor pedunculated from the surface of the upper palpebral tarsal conjunctiva in her left eye. She was histopathologically diagnosed as having sebaceous carcinoma by an excisional biopsy. We performed en bloc resection of the lateral one-third of the posterior lamella including the cutaneous margin of the upper eyelid as well as reconstruction of the defected portion by a switch-flap from the ipsilateral lower eyelid. Histopathologically, because the tumor was restricted to the epithelial region with minimal invasion into the tarsus, we diagnosed the patient to have conjunctival papillary sebaceous carcinoma. Nine months after the surgery, the tumor recurred and was resected and treated by intraoperative mitomycin C. Four months later, the tumor regrew at the resected margins and was treated by resection combined with mitomycin C and cryotherapy. After these combination treatments, the tumor did not recur for at least 1 year postoperatively. CONCLUSION AND IMPORTANCE: Although sebaceous carcinoma usually originates from the meibomian gland cells or less frequently from the Zeis or Moll gland cells, it rarely occurs from bulbar or palpebral conjunctival cells. Because sebaceous carcinoma sometimes shows a pagetoid growth pattern, it can recur even after en bloc resection with a negative study for tumor cells at the surgical margins. The recurrent sebaceous carcinoma cells showed an intraepithelial growth pattern. Considering this superficial growth property, it may be effective to apply intraoperative mitomycin C and cryotherapy treatment combined with surgical resection to reduce the possibility of recurrence of presumed conjunctival papillary sebaceous carcinoma, although mitomycin C alone seems to be insufficient as an adjunctive treatment.