Exploratory open-label clinical study to determine the S-588410 cancer peptide vaccine-induced tumor-infiltrating lymphocytes and changes in the tumor microenvironment in esophageal cancer patients.

Cancer vaccines induce cancer-specific T-cells capable of eradicating cancer cells. The impact of cancer peptide vaccines (CPV) on the tumor microenvironment (TME) remains unclear. S-588410 is a CPV comprising five human leukocyte antigen (HLA)-A*24:02-restricted peptides derived from five cancer testis antigens, DEPDC1, MPHOSPH1, URLC10, CDCA1 and KOC1, which are overexpressed in esophageal cancer. This exploratory study investigated the immunologic mechanism of action of subcutaneous S-588410 emulsified with MONTANIDE ISA51VG adjuvant (median: 5 doses) by analyzing the expression of immune-related molecules, cytotoxic T-lymphocyte (CTL) response and T-lymphocytes bearing peptide-specific T-cell receptor (TCR) sequencing in tumor tissue or blood samples from 15 participants with HLA-A*24:02-positive esophageal cancer. Densities of CD8+, CD8+ Granzyme B+, CD8+ programmed death-1-positive (PD-1+) and programmed death-ligand 1-positive (PD-L1+) cells were higher in post- versus pre-vaccination tumor tissue. CTL response was induced in all patients for at least one of five peptides. The same sequences of peptide-specific TCRs were identified in post-vaccination T-lymphocytes derived from both tumor tissue and blood, suggesting that functional peptide-specific CTLs infiltrate tumor tissue after vaccination. Twelve (80%) participants had treatment-related adverse events (AEs). Injection site reaction was the most frequently reported AE (grade 1, n = 1; grade 2, n = 11). In conclusion, S-588410 induces a tumor immune response in esophageal cancer. Induction of CD8+ PD-1+ tumor-infiltrating lymphocytes and PD-L1 expression in the TME by vaccination suggests S-588410 in combination with anti-PD-(L)1 antibodies may offer a clinically useful therapy.Trial registration UMIN-CTR registration identifier: UMIN000023324.

Proton pump inhibitor after endoscopic resection for esophageal squamous cell cancer: multicenter prospective randomized controlled trial.

BACKGROUND: Whether proton pump inhibitors (PPIs) relieve heartburn or precordial pain after endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this study was to investigate the efficacy of PPI therapy for these symptoms after ER for ESCC. METHODS: We conducted a multicenter prospective randomized controlled trial among 15 hospitals in Japan. In total, 229 patients with cT1a ESCC were randomly assigned to receive PPI therapy for 5 weeks after ER (the PPI group, n = 115) or follow-up without PPI therapy (the non-PPI group, n = 114). The primary end point was the incidence of gastroesophageal reflux disease (GERD)-like symptoms after ER from a self-reported questionnaire (Frequency Scale for Symptoms of GERD). Secondary end points were ulcer healing rate at 5 weeks, incidence of pain, improvement rate of symptoms in those who started PPI therapy because of GERD-like symptoms in the non-PPI group, and adverse events. RESULTS: No significant difference was observed in the incidence of GERD-like symptoms after ER between the non-PPI and PPI groups (30 % vs 34 %, respectively). No significant differences were observed in the ulcer healing rate at 5 weeks (84 % vs 85 %) and incidence of pain within 1 week (36 % vs 45 %). In nine of ten patients (90 %) who started PPI therapy because of GERD-like symptoms in the non-PPI group, PPI administration relieved GERD-like symptoms. No adverse events related to PPI administration were observed. CONCLUSION: PPI therapy is not efficacious in reducing symptoms and did not promote healing of ulcers in patients undergoing ER for ESCC.

Serum prorenin levels and diabetic retinopathy in type 2 diabetes: new method to measure serum level of prorenin using antibody activating direct kinetic assay.

AIM: To investigate the serum levels of prorenin and its correlation with the severity of diabetic retinopathy (DR). METHODS: 248 patients with diabetes and 108 control subjects were divided into four groups: no-DR (n = 146), no proliferative diabetic retinopathy (no-PDR) (n = 78), PDR (n = 24), and controls (n = 108). Serum levels of prorenin from all subjects were measured using the new antibody activating direct kinetic (AAD-PR) assay. The serum prorenin levels were compared among the groups. RESULTS: The serum levels of prorenin in the control, no-DR, no-PDR, and PDR groups, respectively, were 109.1 (66.1), 194.6 (160.4), 271.5 (220.3), and 428.4 (358.4) pg/ml (mean (SD)). Prorenin in the PDR group was remarkably high compared with the control and no-DR groups (p<0.0001) and with the no-PDR group (p = 0.002). Serum levels of prorenin increased with increasingly severe retinopathy. No correlation was found between the prorenin level and the duration of disease or HbA(1c). CONCLUSIONS: The serum levels of prorenin in patients with PDR were found to be markedly high using the AAD-PR assay. Increased levels of prorenin in diabetes may have an important role in the pathogenesis of DR.

Cyanide-bridge Fe-Fe and Fe-Co molecular squares: structures and electrochemistry of

Cyanide-bridged iron-iron and iron--cobalt molecular squares of [Fe(II/4)(mu-CN)4(bpy)8[(PF6)4 x 4H2O (1), [Fe(II/2)Co(II/2)(mu-CN)4(bpy)8](PF6)4 x 3CHCl3 x 2CH3CN (2), and [Fe(II/2)Co(III/2)(mu-CN)4(bpy)8](PF6)6 x 2CHCl3 x 4CH3NO2 (3) (bpy =2,2'-bipyridine) were prepared. X-ray structure analyses for 1-3 were performed and their electrochemistry was studied. In 1-3, four metal ions are bridged by cyanide groups to form tetranuclear macrocycles ("molecular squares"). Each metal ion in the square is six-coordinate: four of the coordination sites are occupied by the nitrogen atoms of two of bpy ligands and the remaining cis coordination sites are occupied by cyanide-carbon or cyanide-nitrogen atoms. In 1, Fe-C (cyanide) (1.899(4)-1.927(4)A) and Fe-N(cyanide) (1.929(4)-1.950(4)A) distances are typical of low-spin Fe2+ ions. In 2, Fe-C(cyanide) and Co(2+)-N(cyanide) bond lengths are in the range 1.919(5)-1.963(5)A and 1.850(5)-2.017(5) A, respectively: in contrast, shorter bond lengths are observed for the metal to cyanide-carbon and cyanide-nitrogen (1.878(7)- 1.893(7) A) in 3. As a result, the molecular squares in 1. 2, and 3 have sides of 4.947(1)4.986(1) A, 5.001(1)-5.053(1) A, and 4.910(1)-4.918(1) A, respectively. Magnetic susceptibility measurements revealed that the Fe2+ and Co3- ions in 1 and 3 are diamagnetic, while the high-spin Co2+ ions in 2 are weakly coupled through the low-spin Fe2 ions. Cyclic voltammograms of the squares are presented, and the electrochemically generated mixed-valent species [Fe(II/2)Fe(III/2)(mu-CN)4(bpy)8]6+ was discussed in terms of the intervalence transfer band.

Vitreous surgery simulator.

OBJECTIVE: To reduce the surgical risks to patients and expose surgeons to surgical experience and complications, we have developed a practical system of vitreous surgery using virtual-reality technology. METHODS: The system is composed of high-resolution color stereo binoculars, haptic devices, foot switches, and a high-speed graphics computer. To simulate vitreous surgery, we created several virtual patient eyes with retinal diseases such as preretinal membranes and subretinal neovascular tissue at the fovea. RESULTS: The simulator provided the trainees with an operating environment similar to an actual one, and allowed them to learn to maneuver surgical instruments and remove proliferative tissue on the retina, under the retina, or both. This system allowed surgeons to avoid iatrogenic complications through visual signs such as retinal hemorrhage when the instrument contacted the retinal surface. CONCLUSIONS: This simulator may not only be suitable for residents to learn ocular surgical techniques but may also allow veteran surgeons to develop new surgical methods and skills.

Scanning laser ophthalmoscope correlations with biomicroscopic findings and foveal function after macular hole closure.

OBJECTIVE: To investigate the relation between foveal findings and visual function in eyes with a resolved idiopathic macular hole after vitreous surgery. METHODS: We divided 28 eyes with postoperative idiopathic macular hole resolution into 3 groups based on postoperative biomicroscopic foveal findings of complete closure, partial closure, or atrophic closure. To evaluate foveal retinal function, scanning laser ophthalmoscope (SLO) microperimetry was performed preoperatively and 6 months postoperatively. RESULTS: Postoperatively in 18 eyes (64%), the foveal images became normal or almost normal and were classified as having complete closure, 6 eyes (21%) were classified as having partial closure, and 4 eyes (14%) as having atrophic closure. The corresponding visual acuity levels 6 months postoperatively were, respectively, 0.10, 0.35, and 0.64 (P<.01) based on LogMAR analysis. Preoperative SLO microperimetry detected an absolute scotoma at the bottom of all macular holes; postoperatively, the absolute scotoma disappeared in the 18 eyes with complete hole closure, but a relative scotoma was detected in 6 eyes. Of 6 eyes with partial closure, 1 had an absolute scotoma and 5 had a relative scotoma. An absolute scotoma was detected in 4 eyes with atrophic closure. CONCLUSIONS: After macular hole closure, SLO findings correlate both with biomicroscopic findings and foveal function. Better anatomical foveal recovery in eyes after macular hole closure results in better improvement of vision than in eyes in which the foveal anatomical findings are not as good.

Effect of corticotropin releasing factor receptor 1 antagonist on extracellular norepinephrine, dopamine and serotonin in hippocampus and prefrontal cortex of rats in vivo.

Corticotropin releasing factor (CRF) is a major mediator of adaptive responsiveness to stress. We measured changes in extracellular concentrations of catecholamine and indoleamines in freely moving rats in response to administration of CRF1 antagonist CP-154,526 by using in vivo microdialysis. Dialysis probes were placed stereotaxically in either the hippocampus or the prefrontal cortex. We examined the response in the hippocampus or the prefrontal cortex to 32.0 mg/kg i.p. administration of CP-154,526. CP-154,526 reduced the extracellular concentration of norepinephrine (NE) from 30 min to 180 min and 5-hydroxytryptamine (5-HT) from 30 min to 60 min after injection in the hippocampus. CP-154,526 did not remarkably change dopamine (DA). There were no significant differences between CP-154,526 and vehicle in NE, 5-HT and DA in the prefrontal cortex. The present results indicate that CRF1 receptor antagonist produced a decrease in dialysate concentration of NE and 5-HT, but not DA, in the hippocampus. These results suggest that the CRH-1 receptor antagonist suppresses the release of NE and 5-HT in the hippocampus.

Suppression of conditioned fear by administration of CCKB receptor antagonist PD135158.

In order to examine the involvement of CCK in the formation of anxiety, we have investigated whether CCKB receptor antagonist PD135158 suppressed conditioned fear stress. Rats were individually subjected to 30 min of inescapable electric footshock in a chamber with a grid floor. First, the rats were individually subjected to 30 min of footshock. Twenty-four h after the footshock, the rats were again placed in the chamber and observed for 5 min without shocks. PD135158 was administered 30 min before placing the rats in the chamber again. Secondly, PD135158 was administered 30 min before footshock. Thirdly, PD135158 was administered 5 min after footshock. Administration of PD135158 30 min before conditioned fear stress significantly reduced freezing behavior. Administration of PD135158 30 min before footshock also significantly reduced freezing behavior. But, administration of PD135158 5 min after footshock did not significantly reduce freezing behavior. PD135158 blocked not only the acquisition but also the expression of conditioned fear. These results suggest that the CCKB receptor might play an important role in conditioned fear stress and that it might be related to anxiety.

Risk of decreased visual acuity in full-thickness idiopathic macular holes.

We studied 169 eyes of 149 patients with a full-thickness idiopathic macular hole to ascertain the risk factors of enlargement of the hole or the surrounding retinal detachment and subsequent decreased visual acuity. Eyes were divided as follows: group A, 48 eyes with no posterior vitreous detachment and a hole 400 microns or smaller; group B, 77 eyes with no posterior vitreous detachment and a hole 400 microns or larger; group C, 13 eyes with posterior vitreous detachment and a hole 400 microns or smaller; group D, 31 eyes with posterior vitreous detachment and a hole 400 microns or larger. In group A, the macular hole enlarged in 37 eyes (77%); the retinal detachment enlarged in 35 eyes (73%); and visual acuity decreased by two or more Snellen lines in 28 eyes (58%). These percentages were significantly higher than those in group B (P = .01, P = .01, and P = .01, respectively), group C (P = .02, P = .01, and P = .01, respectively), and group D (P = .01, P = .05, and P = .01, respectively). Eyes without posterior vitreous detachment with a full-thickness idiopathic macular hole 400 microns or smaller may have a greater risk of an enlarged macular hole, surrounding retinal detachment, and subsequent visual loss.

Role of the vitreous in the prognosis of peripheral uveitis.

We studied 116 eyes with peripheral uveitis (mean follow-up, 5.0 years) to ascertain the effect of the vitreous on prognosis. At the initial examination, the prevalence of partial posterior vitreous detachment was significantly higher in eyes with macular edema (27%) than in those without (7%, P = .01). During follow-up, the prevalence of no posterior vitreous detachment initially was significantly higher in eyes that developed macular edema (78%) than in those that did not (22%, P = .01). The prevalence of no or partial posterior vitreous detachment was also significantly higher in eyes with decreased visual acuity of three or more Snellen lines (57% and 38%, respectively) compared with those with visual acuity decreases of two Snellen lines or less (21% and 11%; P = .02 and P = .01, respectively). Eyes with peripheral uveitis with vitreous adhesion may have a less favorable prognosis compared with those with complete posterior vitreous detachment.

Relationship between floaters, light flashes, or both, and complications of posterior vitreous detachment.

We examined biomicroscopically the vitreous and retinal conditions of 902 consecutive symptomatic eyes (785 patients) to ascertain the relationship between floaters, light flashes, or both, and complications of posterior vitreous detachment. Of 785 patients, 785 symptomatic eyes were divided as follows: group 1, 342 eyes with floaters alone; group 2, 240 eyes with floaters and light flashes; and group 3, 203 eyes with light flashes alone. We also studied 636 asymptomatic fellow eyes. The prevalence of posterior vitreous detachment was significantly higher in groups 1 (138 of 342, 40%), 2 (214 of 240, 89%), and 3 (137 of 203, 67%) than in the asymptomatic eyes (127 of 636, 20%), in group 2 than in groups 1 and 3, and in group 3 than in group 1 (P = .01). The prevalence of retinal breaks in eyes with posterior vitreous detachment was 5% (seven of 138), 13% (27 of 214), 12% (16 of 137), and 4% (five of 127) in groups 1, 2, 3, and the asymptomatic eyes, respectively; the prevalence was significantly higher in groups 2 and 3 than in asymptomatic eyes (P = .02 and P = .04) and group 1 (P = .04 and P = .05). The prevalence of vitreous hemorrhage in eyes with retinal breaks was 71% (five of seven), 70% (19 of 27), and 6% (one of 16) in groups 1, 2, and 3, respectively. Of 117 patients with bilateral symptoms, 105 (90%) had the same symptoms and 104 (89%) had the same vitreoretinal relationship bilaterally.(ABSTRACT TRUNCATED AT 250 WORDS)

Transient shallow anterior chamber induced by supraciliary fluid after vitreous surgery.

PURPOSE: To report the mechanism of transient shallow anterior chamber after vitreous surgery for proliferative diabetic retinopathy. METHOD: Using ultrasound biomicroscopy, we examined a patient with transient shallow anterior chamber after vitreous surgery for proliferative diabetic retinopathy. RESULTS: On the day after surgery, slit-lamp examination disclosed a shallow anterior chamber that persisted for 1 week and deepened thereafter. Ultrasound biomicroscopy 5 days postoperatively disclosed a narrow angle in the peripheral anterior chamber and supraciliary fluid. At 14 days postoperatively, suprachoroidal fluid could not be detected, and the angle was wide. CONCLUSION: The shallow anterior chamber in this patient was caused by supraciliary fluid after vitreous surgery.

Course of vitreomacular traction syndrome.

PURPOSE: Although the course of vitreomacular traction syndrome is necessary to treat patients or to establish the value of the surgical technique, little information is available about its course. In this study, we ascertained the natural history of vitreomacular traction syndrome. METHODS: We retrospectively studied 53 consecutive symptomatic eyes with vitreomacular traction syndrome. RESULTS: In 43 (81%) of 53 eyes with cystoid macular changes at the diagnostic examination, 29 (67%) of 43 had cystoid changes that persisted during the median follow-up period of 60 months. The visual acuities at the time of the final examination decreased two Snellen lines or more from the initial measurement in 34 (64%) of 53 eyes. During the follow-up period, six (11%) of 53 eyes developed complete posterior vitreous detachment. The number of eyes with resolved cystoid changes or stable visual acuity was significantly higher when complete vitreomacular separation occurred (six of six) than when it did not (three [8%] of 37, P = .01; 13 [28%] of 47, P = .01). CONCLUSIONS: Most symptomatic eyes with vitreomacular traction syndrome underwent a further decrease in visual acuity. Complete vitreomacular separation, which occurs infrequently in eyes with the disorder, allows resolution of cystoid changes and improvement of visual acuity.

Effect of the vitreous on the prognosis of full-thickness idiopathic macular hole.

We studied 112 eyes with full-thickness idiopathic macular holes (mean follow-up period, 5.7 years) to ascertain the effect of the vitreous on prognosis. Eyes were divided as follows: group 1, 58 eyes with no posterior vitreous detachment; group 2, 25 eyes with no posterior vitreous detachment initially and development of complete posterior vitreous detachment during follow-up; and group 3, 29 eyes with complete posterior vitreous detachment. In group 1, the macular hole enlarged in 37 eyes (64%), and the surrounding retinal detachment enlarged in 29 (50%); visual acuity decreased in 20 eyes (34%) by two or more Snellen lines. These percentages were significantly higher than in group 3 (14%, 10%, and 10%; P = .01, P = .01, and P = .03, respectively). Eyes with a full-thickness macular hole with no posterior vitreous detachment may have a greater risk of enlargement of the macular hole and surrounding retinal detachment, and thus a worse prognosis than eyes with posterior vitreous detachment.

Prognosis of stage 2 macular holes.

PURPOSE: We ascertained the natural course of stage 2 idiopathic macular holes to determine better treatment possibilities. METHODS: We reviewed 48 eyes with stage 2 idiopathic macular holes and followed them up for more than two years. At each examination, best-corrected Snellen visual acuity was measured by a physician masked to the hypothesis of the study. RESULTS: Stage 2 lesions progressed to stage 3 or 4 during the follow-up period in 32 (67%) and 14 (29%) of 48 eyes, respectively; two eyes (4%) remained in stage 2. In 41 (85%) of 48 eyes, the hole size enlarged during the follow-up: 32 (94%) of 34 eyes had vitreomacular attachment and nine (64%) of 14 eyes had vitreomacular separation at the final examination, for a statistically significant difference in prevalence (P = .03). Visual acuity decreased two or more Snellen lines during the follow-up period in 34 (71%) of 48 eyes, the prevalence of which was significantly higher in eyes with vitreomacular attachment at the final examination (28 of 34, 82%) than in eyes with vitreomacular separation at the final examination (six of 14, 43%) (P = .01). CONCLUSION: Even though vitreomacular separation may improve the prognosis of a macular hole, stage 2 lesions usually will develop an enlarged hole and decreased visual acuity.

Vitreous findings in cases of optic nerve pits and serous macular detachment.

We examined biomicroscopically the relationship between the optic nerve and the vitreous in 17 eyes of 16 consecutive patients with pits of the optic nerve that demonstrated an associated serous detachment of the macula. The posterior vitreous was attached in 15 eyes (88%); the posterior vitreous was partially detached with a vitreous strand terminating at the optic pit in two eyes (12%). Of the 15 eyes without posterior vitreous detachment, 11 (73%) had an anomalous Cloquet's canal that was markedly condensed and terminated at the margin of the pit. During ocular movement, we observed a back-and-forth movement of the anomalous Cloquet's canal and a pulsating translucent membrane that covered the pit. Our findings suggest that the intravitreal traction on the optic pit by the anomalous Cloquet's canal may have a role in the development of macular detachment.

Imaging of epiretinal membranes in macular holes by scanning laser ophthalmoscopy.

PURPOSE: Because recognition and removal of an epiretinal membrane are important in macular hole surgery, we used the scanning laser ophthalmoscope preoperatively to study epiretinal membranes in patients with idiopathic macular holes. METHODS: We studied 67 eyes (60 consecutive patients) with idiopathic macular holes. We evaluated the thickness and the extent of the epiretinal membrane by using a scanning laser ophthalmoscope. We then compared the fundus images obtained with the scanning laser ophthalmoscope with red-free monochromatic fundus photographs. RESULTS: Confocal imaging of the fundus with either argon blue (488 nm) or argon green (514 nm) laser illumination clearly showed the epiretinal membranes. In all eyes, we observed lesions ranging from a patchy glinting light reflex to a dense epiretinal membrane. A well-demarcated dense epiretinal membrane around the macular hole was observed in seven (44%) of 16 eyes with stage 2 macular holes and in 12 (40%) of 30 eyes with stage 3 holes, but in only two (10%) of 21 eyes with stage 4 holes. The prevalence of the dense epiretinal membrane in stage 2 or 3 holes was significantly higher than in stage 4 holes (P = .025 and .024, respectively). CONCLUSIONS: Fundus imaging using the scanning laser ophthalmoscope with argon laser illumination is useful preoperatively to evaluate epiretinal membranes in eyes with idiopathic macular holes.

Spontaneous resolution of foveal detachments and macular breaks.

PURPOSE: To evaluate the mechanism of spontaneous resolution of foveal detachments and idiopathic macular breaks. METHODS: We reviewed the records of 139 consecutive eyes (94 patients) with either a foveal detachment or a macular break in patients who were examined between 1989 and 1992. There were 26 men and 68 women (mean age, 66.9 +/- 6.9 years). They were either unoperated on or observed during the period that preceded surgery. Each patient underwent complete ophthalmic examination in addition to slit-lamp photography of the vitreomacular interface and microperimetry with the scanning laser ophthalmoscope. RESULTS: Eight eyes demonstrated spontaneous resolution. A foveal detachment was noted in five eyes (five patients) and a stage 2 macular break in three eyes (three patients). The mean duration of observation was 33 months (range, one to 144 months). Resolution of the foveal detachments occurred without the development of posterior vitreous detachment. In each eye, the presence of a pseudo-operculum, indicating vitreofoveal separation, was accompanied by flattening of the foveal detachment without detectable posterior vitreous detachment. The three eyes with stage 2 macular break resolved after premature development of a posterior vitreous detachment. CONCLUSIONS: Foveal detachment and macular break resolution seem to result from the release or weakening of vitreous traction on the fovea. Reattachment of the foveal retina preserves fair to good visual acuity. Surgical intervention is contraindicated (1) in eyes in which foveal detachment flattens and develops a pseudo-operculum and (2) when a posterior vitreous detachment develops in an eye with a stage 2 macular break. Careful biomicroscopic vitreous examination and microperimetry with the scanning laser ophthalmoscope are extremely useful methods for adequate examination of these patients.

Inhibitory effect of losartan on laser-induced choroidal neovascularization in rats.

PURPOSE: To investigate the inhibitory effects of losartan, an angiotensin receptor antagonist, on angiogenesis in a rat model of laser-induced choroidal neovascularization. METHODS: Experimental study. Fifteen Brown-Norway male rats received losartan (approximately 5 mg/kg/d) in drinking water, and 15 Brown-Norway male rats received unsupplemented drinking water 1 week before photocoagulation, and it was continued to the end of the study. Two weeks after intense laser photocoagulation, choroidal neovascularization was evaluated by fluorescein angiography and histopathologic evaluation. RESULTS: The incidence of choroidal neovascularization formation was 99.5 +/-.2% (mean +/- standard deviation) in controls and 72.5 +/- 8.8% in losartan-treated rats (P <.01). Quantitative morphometric assessment revealed mean choroidal neovascularization lesion thickness of 54 and 44.8 microm, respectively, in controls and losartan-treated rats (P <.01). CONCLUSION: Losartan seems to inhibit development of laser-induced choroidal neovascularization. Angiotensin receptor antagonists may be useful as prophylaxis against choroidal neovascularization associated with age-related macular degeneration.

Scotoma and fixation patterns using scanning laser ophthalmoscope microperimetry in patients with macular dystrophy.

PURPOSE: We used scanning laser ophthalmoscope microperimetry to evaluate the retinal scotoma and the fixation points in the patients with macular dystrophy. METHODS: We studied 10 eyes of five patients with macular dystrophy (three patients with cone dystrophy and two patients with Stargardt disease). The mean patient age was 37 years (range, 13 to 64 years). An estimation of scotoma and fixation points on the retina was performed using scanning laser ophthalmoscope microperimetry. RESULTS: All 10 eyes (100%) had one of two types of dense scotoma: type one was a dense ring scotoma (five eyes, 50%), and type two was a dense central scotoma (five eyes, 50%) that included the center of the fovea. In all eyes with a dense ring scotoma, the fixation points were stable and did not shift. In all eyes with a dense central scotoma, the fixation shifted. The logarithm of minimal angle of resolution of the visual acuity in the eyes with the dense central scotoma was significantly worse than that of eyes with the dense ring scotoma type (P =.005). CONCLUSIONS: Scanning laser ophthalmoscope microperimetry findings demonstrate two types of dense scotoma (dense ring scotoma and dense central scotoma) in the patients with macular dystrophy. The two types of dense scotoma affect the shifting of the fixation points and the stability of fixation and may result in the difference in visual acuity in the patients with macular dystrophy.