Pilot Assessment of the Repeatability of Indocyanine Green Fluorescence Imaging and Correlation with Traditional Foot Perfusion Assessments.

BACKGROUND: Ankle brachial index (ABI), toe pressures (TP), and transcutaneous oxygen pressure (TcPO2) are traditionally used in the assessment of critical limb ischemia (CLI). Indocyanine green (ICG) fluorescence imaging can be used to evaluate local circulation in the foot and to evaluate the severity of ischemia. This prospective study analyzed the suitability of a fluorescence imaging system (photodynamic eye [PDE]) in CLI. MATERIAL AND METHODS: Forty-one patients with CLI were included. Of the patients, 66% had diabetes and there was an ischemic tissue lesion in 70% of the limbs. ABI, toe pressures, TcPO2 and ICG-fluorescence imaging (ICG-FI) were measured in each leg. To study the repeatability of the ICG-FI, each patient underwent the study twice. After the procedure, foot circulation was measured using a time-intensity curve, where T1/2 (the time needed to achieve half of the maximum fluorescence intensity) and PDE10 (increase of the intensity during the first 10 s) were determined. A time-intensity curve was plotted using the same areas as for the TcPO2 probes (n=123). RESULTS: The mean ABI was 0.43, TP 21 mmHg, TcPO2 23 mmHg, T1/2 38 s, and PDE10 19 AU. Time-intensity curves were repeatable. In a Bland-Altman scatter plot, the 95% limits of agreement of PDE10 was 9.9 AU and the corresponding value of T1/2 was 14 s. Correlation between ABI and TP was significant (R=.73, p<.001), and it was weaker in diabetic patients (R=.47, p=.048) compared with non-diabetic patients (R=.89, p=.002). Correlations between ABI and TcPO2 and TP and TcPO2 were weak (R=.37, p=.05 and R=.43, p=.037, respectively). Correlation between TcPO2 and PDE10 was strong in diabetic patients (R=.70, p=.003). CONCLUSIONS: According to this pilot study, ICG-FI with PDE can be used in the assessment of blood supply in the ischemic foot.

Bilateral central retinal artery occlusion and vein occlusion complicated by severe choroidopathy in systemic lupus erythematosus.

Severe retinal vascular occlusions resulting in blindness is a rare occurrence in patients with systemic lupus erythematosus (SLE). Herein, we report a case of a 33-year-old female who developed combined central retinal artery occlusion, retinal vein occlusion, and choroidopathy and rapidly became completely blind in both eyes within a week. The electroretinogram revealed a severely attenuated a-wave and b-wave, indicating a profound dysfunction of both choroidal and retinal circulation, respectively. The current case demonstrates objectively the functional impact of severe choroidopathy in SLE for the first time. Patients with unilateral blindness due to combined retinal/choroidal vascular obstructions should be monitored carefully to ensure adequate anticoagulant therapy in an attempt to guard the vision in the fellow eye.

Survival and axonal regeneration of off-center retinal ganglion cells of adult cats are promoted with an anti-glaucoma drug, nipradilol, but not BDNF and CNTF.

OFF-center retinal ganglion cells (RGCs) occupy a smaller proportion than ON RGCs when RGCs regenerate axons into a transplanted peripheral nerve. We examined whether the regeneration ability of OFF RGCs in adult cats was promoted when the numbers of regenerating RGCs were increased with brain-derived neurotrophic factor (BDNF)+ciliary neurotrophic factor (CNTF)+forskolin (BCF) or 3,4-dihydro-8-(2-hydroxy-3-isopropylamino)-propoxy-3-nitroxy-2H-1-benzopyran (nipradilol), an anti-glaucoma drug. ON or OFF RGCs were morphologically determined on the basis of their dendritic ramification in the inner plexiform layer using computational analysis. In the normal intact retina the ratio of ON and OFF RGCs (ON/OFF ratio) was 1.25 (55%/44%); whereas, it was 2.61 in regenerating RGCs with saline injection (control) 6 weeks after peripheral nerve transplantation. Estimated numbers of regenerating ON and OFF RGCs were 2149 and 895, respectively. An injection of BCF increased only numbers of ON RGCs into 5766 (2.7-fold to control) but not that of OFF RGCs, n=858. Nipradilol increased both estimated numbers of ON (11,518, 5.4-fold to control) and OFF RGCs (7330, 8.2-fold to control). In the retinas with optic nerve (OpN) transection and intravitreal saline-, BCF- or nipradilol-injection, numbers of ON and OFF RGCs surviving axotomy showed similar trend to that in regenerating RGCs. Thus, nipradilol promoted the survival and regeneration abilities of both of ON and OFF RGCs whereas BCF only did the abilities of ON RGCs. The distribution of tropo-myosin-related kinase B, BDNF receptor, was sparser in the outer two thirds of inner plexiform layer. The lower surviving ability of OFF-RGCs may be attributed in part to the distribution.

Comparison of indocyanine green angiography and optical coherence tomographic angiography in polypoidal choroidal vasculopathy.

PurposeTo compare optical coherence tomographic angiography (OCTA) and indocyanine green angiography (ICGA) images for detecting polypoidal lesions (PLs) and branching vascular networks (BVNs), and to measure the polypoidal areas (PAs) in patients with polypoidal choroidal vasculopathy (PCV).MethodsAll patients underwent ICGA, optical coherence tomography (OCT), and OCTA. We compared the detection sensitivity for PL and BVN, as evaluated by the ICGA and OCTA images. Furthermore, PA measured by ICGA was divided into two groups: one in which the area could be measured by OCTA (ICGA+OCTA+) and the other in which the area could not be measured by OCTA (ICGA+OCTA-).ResultsTwenty-one consecutive eyes of 21 patients (mean age, 73.8±9.8 years) were included. ICGA detected PL in all eyes (100%), whereas OCTA detected PL in 16 eyes (75.2%); ICGA detected BVN in 15 eyes (71.4%), whereas OCTA detected BVN in 20 eyes (95.2%). The mean PA in ICGA+OCTA+ and ICGA+OCTA- was 0.24±0.04 and 0.14±0.01 mm2, respectively; a significant difference was observed between ICGA+OCTA+ PA and ICGA+OCTA- PA (P<0.0001). In addition, the mean PA in the ICGA+OCTA+ group measured by ICGA and OCTA was 0.24±0.04 was 0.19±0.04 mm2, respectively; these values were significantly different (P=0.0046).ConclusionsOCTA might detect more BVNs and fewer PLs compared with ICGA, and PL detected by OCTA might be smaller than those detected by ICGA.

Seasonal variations of acute massive submacular haemorrhage associated with age-related macular degeneration.

AIMS: To determine whether there is a seasonal variation in the onset of acute, massive submacular haemorrhage associated with age-related macular degeneration. METHODS: Sixty eyes of 59 patients diagnosed between April 1998 and March 2005, were studied retrospectively. For each patient, the month and season of onset of the submacular haemorrhage and the mean monthly ambient temperature in Nagoya were analysed. Any history of systemic hypertension was also recorded, and the seasonal variations were also investigated in hypertensive and non-hypertensive groups. RESULTS: The number of cases peaked in winter with a trough in summer, and this seasonal variation was significant (Roger's R = 12.03, p<0.01). The monthly incidence was inversely correlated with the temperature (Spearman's rank correlation coefficient r = 0.89, p<0.01). The seasonal variations were significant in the hypertensive group but not in the non-hypertensive group. CONCLUSION: The considerable seasonal variations suggests that the mechanism for the haemorrhage is strongly correlated with the systemic blood pressure.

Structural organization of the gene for CD40 ligand: molecular analysis for diagnosis of X-linked hyper-IgM syndrome.

CD40 ligand (CD40L) on activated T cells plays a crucial role for Ig heavy-chain class switching and the mutation of the gene for this ligand in the X-chromosome causes immunodeficiency with hyper-IgM (X-HIM). We isolated and characterized the human genomic clone for CD40 L to obtain information about the transcriptional regulatory regions of the gene and to develop a molecular diagnostic method for X-HIM patients. The genomic DNA isolated was over 12 kb long containing 5 exons that cover full sequence of mRNA for the ligand. DNA motif analysis based on transcription factor database revealed the presence of a GATA 1 box at around -265 bp. The typical TATA box, CAT site or GC rich region was not found in the 5' flanking region. However, two possible TATA like sequences were found at around -27 and -136 bp. Using the oligonucleotide primers corresponding to the introns, we performed a PCR-SSCP analysis of each exon from a patient with X-HIM syndrome and detected abnormality in exon 5. When sequenced, dinucleotide deletion in this exon was found in the patient and in one X allele of his mother as the only different sequence from that of the control gene. This procedure is simple and could be used for diagnosis of the X-HIM syndrome.

The inhibitory effect on neurite outgrowth of motoneurons exerted by the ligands ELF-1 and RAGS.

Eph-related receptor tyrosine kinases and ligands are expressed at high levels in the developing nervous system, giving rise to the proposal that they are involved in neuronal connection. Cek8 was found to be predominantly expressed on a subset of motoneurons innervating limb but not body muscles during motoneuron axonal growth. Here we show that the ligands RAGS and ELF-1 were expressed in limb buds and that they activated Cek8 when presented in membrane-bound or clustered forms of Fc chimeric proteins but not in unclustered soluble forms. When chick embryonic motoneurons enriched by panning were cultured on clustered forms of RAGS-Fc and ELF-1-Fc, the neutrite growth of motoneurons expressing Cek8 was inhibited. Our results show a relationship between receptor phosphorylation and neurite growth inhibition and suggest that Eph-related kinases and ligands have a regulatory effect on the axon growth of motoneurons during development.

Simple and reliably sensitive diagnosis and monitoring of Philadelphia chromosome-positive cells in chronic myeloid leukemia by interphase fluorescence in situ hybridization of peripheral blood cells.

Philadelphia (Ph) chromosome or the bcr/abl fusion gene is the hallmark of chronic myeloid leukemia (CML) and serves as a prognostic marker during its treatment. Its detection has been primarily done by karyotype analysis of bone marrow cells. The major limitation of the karyotypic technique is an absolute need for metaphases, often difficult to obtain in an appropriate number in patients under therapy. Fluorescence in situ hybridization (FISH) is a sensitive and quantitative method to detect the bcr/abl fusion gene in cells in both metaphase and interphase. Using M-bcr and abl probes, we performed the interphase FISH in the peripheral blood of 30 healthy volunteers and in 20 hematologically normal bone marrow samples. False-positive cells were detected in 2.7 +/- 0.7% (mean +/- standard deviation) and 2.3 +/- 0.7% among 500 cells, respectively. Then we tested 31 patients with CML at various stages of disease on 50 occasions. Although there was a good correlation between the percentage of FISH-positive cells in the peripheral blood and that in the bone marrow (r = 0.977), between the percentage of FISH-positive cells in the peripheral blood and that of Ph chromosome in the bone marrow (r = 0.841), and between the percentage of FISH-positive cells and that of Ph chromosome in the bone marrow (r = 0.933), the limits of agreement in each group were not small, and thus the peripheral blood FISH test can not be interpreted as the same method with conventional karyotyping. Additionally, we could easily rule out CML in 15 individuals with leukocytosis without performing bone marrow aspiration. The present study indicates that FISH analysis in the peripheral blood is a simple and reliably sensitive test for the detection and quantitative monitoring of the M-bcr/abl fusion gene in CML in routine clinical practice, although this can not entirely replace karyotype analysis of bone marrow cells.

Multicenter observational study comparing sedation/analgesia protocols for laser photocoagulation treatment of retinopathy of prematurity.

OBJECTIVE: The aim of this study was to identify the best sedation/analgesia protocol for laser photocoagulation (PC) of retinopathy of prematurity (ROP). STUDY DESIGN: This multicenter observational study included five hospitals, each using a specific sedation/analgesia protocol: local anesthesia with oxybuprocaine hydrochloride (Group L); intravenous pentazocine (Group P); intravenous fentanyl (Group F); air, oxygen and sevoflurane (AOS) inhalation (Group I). The groups were compared for pain responses, vital signs and adverse events. RESULTS: Heart rates and systemic blood pressures were elevated by PC in Groups L and P and Groups L, P and F, respectively. Moreover, poor analgesic efficacy was recognized in Groups L, P and F. In contrast, Group I experienced hypothermia, enteral feeding intolerance and apnea more frequently. CONCLUSION: From the viewpoint of sedation/pain relief, AOS anesthesia should be the best protocol. However, considering all the various factors together, the most reasonable one can be varied based on the patient's condition and hospital.

Macrophage- and RIP3-dependent inflammasome activation exacerbates retinal detachment-induced photoreceptor cell death.

Detachment of photoreceptors from the retinal pigment epithelium is seen in various retinal disorders, resulting in photoreceptor death and subsequent vision loss. Cell death results in the release of endogenous molecules that activate molecular platforms containing caspase-1, termed inflammasomes. Inflammasome activation in retinal diseases has been reported in some cases to be protective and in others to be detrimental, causing neuronal cell death. Moreover, the cellular source of inflammasomes in retinal disorders is not clear. Here, we demonstrate that patients with photoreceptor injury by retinal detachment (RD) have increased levels of cleaved IL-1ß, an end product of inflammasome activation. In an animal model of RD, photoreceptor cell death led to activation of endogenous inflammasomes, and this activation was diminished by Rip3 deletion. The major source of Il1b expression was found to be infiltrating macrophages in the subretinal space, rather than dying photoreceptors. Inflammasome inhibition attenuated photoreceptor death after RD. Our data implicate the infiltrating macrophages as a source of damaging inflammasomes after photoreceptor detachment in a RIP3-dependent manner and suggest a novel therapeutic target for treatment of retinal diseases.

Sex-determining gene(s) on distal 9p: clinical and molecular studies in six cases.

We report on clinical and molecular findings in five karyotypic males (cases 1-5) and one karyotypic female (case 6) with distal 9p monosomy. Cases 1-3 and 6 had female external genitalia, case 4 showed ambiguous external genitalia, and case 5 exhibited male external genitalia with left cryptorchidism and right intrascrotal testis. Gonadal explorations at gonadectomy in cases 3 and 4 revealed that case 3 had left streak gonad and right agonadism, and case 4 had bilateral hypoplastic testes. Endocrine studies in cases 1-4 and 6 showed that cases 1, 3, and 6 had definite primary hypogonadism, with basal FSH levels of 54, 39, and 41 IU/L, respectively, whereas case 2 with severe malnutrition was unremarkable for the baseline values, and case 4 had fairly good testicular function. Fluorescence in situ hybridization and microsatellite analyses demonstrated that all cases had hemizygosity of the 9p sex-determining region distal to D9S1779, with loss of the candidate sex-determining genes DMRT1 and DMRT2 from the abnormal chromosome 9. Sequence analysis in cases 1-4 and 6 showed that they had normal sequences of each exon of DMRT1 and the DM domain of DMRT2 on the normal chromosome 9, and that cases 1-4 had normal SRY sequence. The results provide further support for the presence of a sex-determining gene(s) on distal 9p and favor the possibility of DMRT1 and/or DMRT2 being the sex-determining gene(s). Furthermore, as hemizygosity of the 9p sex-determining region was associated with a wide spectrum of gonadogenesis from agonadism to testis formation in karyotypic males and with primary hypogonadism regardless of karyotypic sex, it is inferred that haploinsufficiency of the 9p sex-determining gene(s) primarily hinders the formation of indifferent gonad, leading to various degrees of defective testis formation in karyotypic males and impaired ovary formation in karyotypic females.

Skeletal features and growth patterns in 14 patients with haploinsufficiency of SHOX: implications for the development of Turner syndrome.

We report on clinical features in 14 Japanese patients (4 males and 10 females) with partial monosomy of the short arm pseudoautosomal region involving SHOX (n = 11) or total monosomy of the pseudoautosomal region with no involvement of disease genes on the sex-differential regions (n = 3). Skeletal assessment showed that three patients had no discernible skeletal abnormalities, one patient exhibited short 4th metacarpals and borderline cubitus valgus, and the remaining 10 patients had Madelung deformity and/or mesomelia characteristic of Léri-Weill dyschondrosteosis (LWD), together with short 4th metacarpals and/or cubitus valgus. Skeletal lesions were more severe in females and became obvious with age. Growth evaluation revealed that patients without LWD grew along by the -2 SD growth curve before puberty and showed a normal or exaggerated pubertal growth spurt, whereas those with LWD grew along by the standard growth curves before puberty but exhibited an attenuated pubertal growth spurt and resultant short stature. Maturational assessment indicated a tendency of relatively early maturation in patients with LWD. There was no correlation between the clinical phenotype and the deletion size. These findings suggest that haploinsufficiency of SHOX causes not only short stature but also Turner skeletal anomalies (such as short 4th metacarpals, cubitus valgus, and LWD) and that growth pattern is primarily dependent on the presence or absence of LWD. Because skeletal lesions have occurred in a female-dominant and age-influenced fashion, it is inferred that estrogens exert a maturational effect on skeletal tissues that are susceptible to premature fusion of growth plates because of haploinsufficiency of SHOX, facilitating the development of skeletal lesions.

Structure, expression, and chromosomal localization of the human gene encoding a germinal center-associated nuclear protein (GANP) that associates with MCM3 involved in the initiation of DNA replication.

A 210kDa protein named GANP is upregulated in germinal center (GC)-B cells in the spleen of antigen-immunized mouse. We studied a human ganp gene (hganp) encoding a putative polypeptide of 1980 amino acids. The carboxyl-terminal 721-amino-acid sequence of hGANP is identical to Map80, that is presumably generated by alternative splicing of hganp/Map80 gene. The genomic segment carrying hganp and Map80 genes was isolated, and the chromosomal location was determined on 21q22.3. Northern blot analysis with RNAs from various organs demonstrated a single band of 7kb hganp mRNA, which suggests a preferential transcription of hganp gene from the hganp/Map80 locus. The hGANP expression was upregulated in GCs of the tonsil, as demonstrated by in-situ RNA hybridization and immunohistochemical analyses. The hGANP, with the domain (Map-box) capable of binding to MCM3 in B cells, might be involved in regulation of cell-cycle progression and DNA replication of GC-B cells.

S-cone pathway sensitivity in diabetes measured with threshold versus intensity curves on flashed backgrounds.

PURPOSE: To study sensitivity loss to short wavelength lights in patients with diabetes with or without retinopathy and to identify changes that cannot be attributed to preretinal screening. METHODS: Flash-on-flash thresholds were measured in 41 patients with diabetes and were compared to those in age-matched normals. A 50-ms, 1 degree blue test spot was presented simultaneously with a 500-ms, 2 degree blue flash. A bright yellow background isolated the S-cone system. RESULTS: The mean flash-on-flash threshold curve shifted up as the stage of retinopathy progressed in 16 patients with insulin-dependent diabetes mellitus (IDDM), including those without retinopathy. In 25 patients with noninsulin-dependent diabetes mellitus (NIDDM), those with preproliferative retinopathy revealed sensitivity loss; however, those with background retinopathy or without retinopathy showed no statistically significant change in sensitivity. CONCLUSIONS: The pattern of sensitivity loss in the patients with IDDM cannot be caused by changes in preretinal screening, including yellowing of the lens. Further, early functional changes in the patients with IDDM without retinopathy can be detected by this method.

Novel CACNA1F mutations in Japanese patients with incomplete congenital stationary night blindness.

PURPOSE: Although it was reported that congenital stationary night blindness (CSNB) could be divided into complete and incomplete CSNB clinically in 1986, it was not until 1998 that the two types were found to be distinct clinical diseases by molecular genetic analysis. The purpose of this article is to report mutations in the retina-specific calcium channel alpha1-subunit gene (CACNA1F) in Japanese patients with incomplete CSNB and to describe the clinical features of these patients. METHODS: Seven patients from five separate Japanese families with incomplete CSNB were examined. Genomic DNA was extracted from leukocytes of the peripheral blood, and all 48 exons of the CACNA1F were amplified by polymerase chain reaction and directly sequenced. A complete ophthalmic examination was performed, including best corrected visual acuity, slit lamp and fundus examinations, fundus photography, and electroretinography. RESULTS: A mutation in the CACNA1F was identified in all the patients. The identified mutations were a missense mutation (Gly609Asp); a nonsense mutation (Arg913stop); a splice donor site mutation of G to C at nucleotide 2571+1; a G insertion at nucleotide 709, resulting in a frame shift with a predicted stop codon at codon 247; and a 4-bp deletion at nucleotides 271 to 274, with a replacement by an abnormal 34-bp sequence. Clinically, each patient had essentially normal fundi, mildly reduced corrected visual acuity, and slight myopia or hyperopia with astigmatism. Electrophysiologically, the mixed rod-cone ERG showed a negative configuration with recordable oscillatory potentials. The rod ERG was recordable but subnormal, and the cone and 30-Hz flicker ERGs were markedly depressed. CONCLUSIONS: Five novel mutations were identified in the CACNA1F in five Japanese families with incomplete CSNB, leading to the conclusion that in most Japanese patients, incomplete CSNB is caused by a CACNA1F mutation.

Scotopic threshold response in complete and incomplete types of congenital stationary night blindness.

PURPOSE: To study the function of the rod visual pathway in the complete and incomplete types of congenital stationary night blindness (CSNB), with special reference to the scotopic threshold response (STR) of electroretinograms (ERGs) METHODS: Using full-field stimuli with light intensities ranging from near absolute threshold to bright, ERG intensity series from two patients with complete CSNB, four patients with incomplete CSNB, and four normal subjects were recorded. RESULTS: Neither the rod b-wave nor the STR was recordable from the patients with complete CSNB. In the patients with incomplete CSNB, the STR was clearly recorded, although the absolute threshold was elevated in accordance with elevation of the psychophysical absolute threshold. The b-wave stimulus threshold was not elevated, and the b-wave amplitude near the threshold was normal. The peak time of the STR was delayed by approximately 80 msec, whereas that of the b-wave was normal. CONCLUSIONS: These STR results indicate that the rod system abnormality in complete CSNB differs from that in incomplete CSNB. Furthermore, the greatly delayed peak time of STR in the patients with incomplete CSNB made the interaction between b-wave and STR different from that in normal subjects.

A high association with cone dystrophy in Fundus albipunctatus caused by mutations of the RDH5 gene.

PURPOSE: To analyze the RDH5 gene in patients with fundus albipunctatus with and without cone dystrophy and to determine whether the disease is stationary or progressive and whether the cone dystrophy is a part of fundus albipunctatus or a separate disease. METHODS: Fourteen patients from 12 separate Japanese families with fundus albipunctatus were examined. Six of the patients from 6 families also had a cone dystrophy. Genomic DNA was extracted from leukocytes of the peripheral blood, and exons 2, 3, 4, and 5 of the RDH5 gene were amplified by polymerase chain reaction and were directly sequenced. A complete ophthalmic examination was performed including best-corrected visual acuity, slit-lamp examination, indirect ophthalmoscopy, fundus photography, and electroretinography. RESULTS: In all the patients, either a homozygous mutation or compound heterozygous mutations in the RDH5 gene were identified. The identified mutations were nucleotide position (nt) 103 G to A (Gly35Ser), nt 319 G to C (Gly107Arg), nt 394 G to A (Val132Met), nt 719 G insertion (frame shift), nt 839 G to A (Arg280His), nt 841 T to C (Tyr281His), and nt 928 C to GAAG (Leu310 to GluVal). All these mutations except the Arg280His were new. The nt 928 C to GAAG mutation was detected in patients with and without cone dystrophy. Cone dystrophy was most frequently seen in patients over 40 years old. CONCLUSIONS: Fundus albipunctatus either with or without cone dystrophy is caused by mutations of the RDH5 gene. Cone dystrophy is frequently observed in elderly patients with fundus albipunctatus. The conclusion was reached that the mutations of the RDH5 gene caused a progressive cone dystrophy as well as night blindness.

Multifocal electroretinogram in occult macular dystrophy.

PURPOSE: Occult macular dystrophy (OMD) is an unusual macular dystrophy presenting with an essentially normal fundus and fluorescein angiography but with progressive central visual loss. The authors studied the function of local retinal areas in the posterior pole of patients with OMD using multifocal electroretinograms (ERGs). METHODS: Multifocal ERGs were recorded using the Visual Evoked Response Imaging System with 61 hexagonal elements within a visual field of 30 degrees radius from 8 OMD patients and 20 age-matched, normal subjects. The amplitudes and implicit times of the patients and normal control subjects were compared at the various retinal eccentricities. RESULTs. The amplitudes of the multifocal ERGs in the OMD patients were markedly reduced in the central 7 degrees of the fovea. The difference of the ERG amplitudes between OMD and normal subjects became smaller toward the peripheral retina. Most OMD patients had slight but significantly delayed implicit times across the whole testing field, and the differences between the OMD and the normal subjects did not change with retinal eccentricity. CONCLUSIONS: Our results for multifocal ERG amplitudes support the idea that OMD patients have localized retinal dysfunction distal to the ganglion cells in the central retina. The delayed implicit times across the whole test field suggest that the retinal dysfunction has a broader boundary than expected by ERG amplitudes and psychophysical perimetric results.

Focal macular ERGs in eyes after removal of macular ILM during macular hole surgery.

PURPOSE: The removal of the internal limiting membrane (ILM) for traction maculopathy has recently been advocated. However, it is generally believed that the ILM plays an important role in retinal function, because it is the basal lamina of the Müller cells that are involved in the generation of the electroretinogram (ERG) b-wave. To date, there has been no objective assessment of retinal function on removing the ILM. In this study, the changes of each component of the focal macular electroretinograms (FMERGs) were investigated in eyes before and after the ILM was removed in the macular area during surgery for idiopathic macular holes (IMHs). METHODS: FMERGs were elicited by a 15 degrees stimulus centered on the fovea and monitored by an infrared fundus camera. FMERGs were recorded from 49 eyes of 48 patients with IMHs before and 6 weeks after anatomically successful macular hole surgery. Whether an eye had or did not have the ILM removed was randomly determined. The ILM was removed in 30 eyes (ILM-off group) and was not removed in 19 eyes (ILM-on group). Six months after surgery, the same examination was performed in 27 eyes of the ILM-off group and in 15 eyes of the ILM-on group. The amplitudes and implicit times of the a- and b-waves and the mean amplitudes and implicit times of the first three oscillatory potentials (OP1 to OP3) were compared before and after surgery within and between the groups. RESULTS: Visual acuity increased significantly after surgery in both groups. In the ILM-on group, the amplitude of the a- and b-waves and the OPs increased significantly 6 months after surgery (P: = 0.0093, P: = 0.0019, P: = 0.0024, respectively, paired t-test). In the ILM-off group, the a-wave amplitude and mean OP amplitudes were significantly larger 6 months after surgery (P: = 0.0077, P: = 0.0030, respectively, paired t-test). The b-wave amplitude, however, did not change significantly. The percentage increase in the b-wave amplitude 6 months after surgery was significantly higher in the ILM-on group (44.0%) than in the ILM-off group (15.0%; P: = 0.037, t-test). CONCLUSIONS: The removal of the ILM had no adverse effect on visual acuity. However, the selective delay of recovery of the FMERG b-wave 6 months after surgery suggests an alteration of retinal physiology in the macular region.

Multifocal ERG findings in complete type congenital stationary night blindness.

PURPOSE: To study the multifocal electroretinogram (mfERG) in patients with the complete type of congenital stationary night blindness (cCSNB), which is thought to be due to a defect in neurotransmission from the photoreceptors to the ON-bipolar cells. METHODS: mfERGs were recorded with the VERIS recording system from four patients with cCSNB, none of whom had nystagmus. The stimulus array consisted of 61 hexagons, and the total recording time was approximately 4 minutes. The amplitudes and implicit times of the first- and second-order kernels of the local responses were compared with those from 20 myopic controls. Waveforms of the summed response from all locations were also compared between the two groups. RESULTS: The first-order kernels of the mfERGs of cCSNB patients had normal amplitudes but delayed implicit times for nearly the whole field tested. The second-order kernel was severely attenuated in amplitude in cCSNB patients. The ratios of the second- to first-order kernel amplitudes were significantly reduced in cCSNB and clearly separated the cCSNB group from the control group without any overlap of the values. CONCLUSIONS: The second-order kernel, which is involved in adaptative mechanism of the retina to repeated flashes, is selectively reduced in cCSNB. The delay of the implicit times of the first-order kernel in patients with cCSNB may be related to the severe amplitude reduction of the second-order kernel.