Esophageal squamous cell carcinoma-precursor lesions and early diagnosis

Squamous cell carcinoma of the esophagus (SCCE) carries a poor prognosis due to late diagnosis.Early detection is highly desirable,since surgical and endoscopic resection offers the only possible cure for esophageal cancer.Population screening should be undertaken in high risk areas,and in low or moderate risk areas for people with risk factors (alcoholics,smokers,mate drinkers,history of head and neck cancer,achalasia and lye stricture of the esophagus).Esophageal balloon cytology is an easy and inexpensive sampling technique,but the current methods are insufficient for primary screening due to sampling errors.Conventional endoscopy with biopsy remains the standard procedure for the identification of pre-malignant and early malignant changes in esophageal mucosa and endoscopic detection.It may be enhanced by several techniques such as dye and optic chromoendoscopy,magnifying endoscopy,and optical-based spectroscopic and imaging modalities.Since more than 80% of SCCE deaths occur in developing countries,where expensive techniques such as narrow band imaging (NBI) and autofluorescence imaging are unavailable,the most cost-effective tool for targeting biopsies may be Lugol dye chromoendoscopy,since it is easy,accurate,inexpensive and available worldwide.In ideal conditions,or in developed countries,is it reasonable to think that optimal detection will require a combination of techniques,such as the combination of Lugol’s chromoendoscopy and NBI to identify esophageal areas that require further characterization by a high resolution technique.The efficacy and cost-effectiveness will determine whether these modalities will become part of standard endoscopy practice.

Autofluorescence excitation-emission matrices for diagnosis of colonic cancer

AIM: To investigate the autofluorescence spectroscopic differences in normal and adenomatous coionic tissues and to determine the optimal excitation wavelengths for subsequent study and clinical application. METHODS: Normal and adenomatous coionic tissues were obtained from patients during surgery. A FL/FS920 combined TCSPC spectrofluorimeter and a lifetime spectrometer system were used for fluorescence measurement. Fluorescence excitation wavelengths varying from 260 to 540 nm were used to induce the autofluorescence spectra, and the corresponding emission spectra were recorded from a range starting 20 nm above the excitation wavelength and extending to 800 nm. Emission spectra were assembled into a three-dimensional fluorescence spectroscopy and an excitation-emission matrix (EEM) to exploit endogenous fluorophores and diagnostic information. Then emission spectra of normal and adenomatous coionic tissues at certain excitation wavelengths were compared to determine the optimal excitation wavelengths for diagnosis of coionic cancer. RESULTS: When compared to normal tissues, low NAD (P)H and FAD, but high amino acids and endogenous phorphyrins of protoporphyrin IX characterized the high-grade malignant coionic tissues. The optimal excitation wavelengths for diagnosis of coionic cancer were about 340, 380, 460, and 540 nm. CONCLUSION: Significant differences in autofluorescence peaks and its intensities can be observed in normal and adenomatous coionic tissues. Autofluorescence EEMs are able to identify coionic tissues.

Efficacy of a novel auto-fluorescence imaging system with computer-assisted color analysis for assessment of colorectal lesions

AIM:To evaluate the efficacy of computer-assisted color analysis of colorectal lesions using a novel auto-fluorescence imaging(AFI)system to distinguish neoplastic lesions from non-neoplastic lesions and to predict the depth of invasion.METHODS:From January 2013 to April 2013,consecutive patients with known polyps greater than 5 mm in size who were scheduled to undergo endoscopic treatment at The Jikei University Hospital were prospectively recruited for this study.All lesions were evaluated using a novel AFI system,and color-tone sampling was performed in a region of interest determined from narrow band imaging or from chromoendoscopy findings without magnification.The green/red(G/R)ratio for each lesion on the AFI images was calculated automatically using a computer-assisted color analysis system that permits real-time color analysis during endoscopic procedures.RESULTS:A total of 88 patients with 163 lesions were enrolled in this study.There were significant differences in the G/R ratios of hyperplastic polyps(non-neoplastic lesions),adenoma/intramucosal cancer/submucosal(SM)superficial cancer,and SM deep cancer(P<0.0001).The mean±SD G/R ratios were 0.984±0.118in hyperplastic polyps and 0.827±0.081 in neoplastic lesions.The G/R ratios of hyperplastic polyps were significantly higher than those of neoplastic lesions(P<0.001).When a G/R ratio cut-off value of>0.89 was applied to determine non-neoplastic lesions,the sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),and accuracy were 83.9%,82.6%,53.1%,95.6%and 82.8%,respectively.For neoplastic lesions,the mean G/R ratio was 0.834±0.080 in adenoma/intramucosal cancer/SM superficial cancer and 0.746±0.045 in SM deep cancer.The G/R ratio of adenoma/intramucosal cancer/SM superficial cancer was significantly higher than that of SM deep cancer(P<0.01).When a G/R ratio cut-off value of<0.77 was applied to distinguish SM deep cancers,the sensitivity,specificity,PPV,NPV,and accuracy were80.0%,84.4%,29.6%,98.1%and 84.1%,respectively.CONCLUSION:The novel AFI system with color analysis was effective in distinguishing non-neoplastic lesions from neoplastic lesions and might allow determination of the depth of invasion.

Autofluorescence imaging endoscopy for identifi cation and assessment of inflammatory ulcerative colitis

AIM:To validate the clinical relevance of autofluores-cence imaging(AFI)endoscopy for the assessment of inflammatory ulcerative colitis(UC).METHODS:A total of 572 endoscopic images were se-lected from 42 UC patients:286 taken with white light imaging(WLI)and 286 with AFI from the same sites.WLI images were assessed for overall mucosal inflammation according to Mayo endoscopic subscore(MES),and for seven characteristic endoscopic features.Likewise,AFI photographs were scored according to relative abundance of red,green and blue color com-ponents within each image based on an RGB additive color model.WLI and AFI endoscopic scores from the same sites were compared.Histological evaluation of biopsies was according to the Riley Index.RESULTS:Relative to red(r=0.52,P<0.01)or blue(r=0.56,P<0.01)color component,the green color component of AFI(r=-0.62,P<0.01)corresponded more closely with mucosal inflammation sites.There were signif icant differences in green color components between MES-0(0.396±0.043)and MES-1(0.340± 0.035)(P<0.01),and between MES-1 and ≥ MES-2(0.318±0.037)(P<0.01).The WLI scores for "vascu-lar patterns"(r=-0.65,P<0.01),"edema"(r=-0.62,P<0.01),histology scores for "polymorphonuclear cells in the lamina propria"(r=-0.51,P<0.01)and "crypt architectural irregularities"(r=-0.51,P<0.01)showed correlation with the green color component of AFI.There were significant differences in green color components between limited(0.399± 0.042)and extensive(0.375±0.044)(P=0.014)polymorpho-nuclear cell inf iltration within MES-0.As the severity of the mucosal inflammation increased,the green color component of AFI decreased.The AFI green color com-ponent was well correlated with the characteristic en-doscopic and histological inflammatory features of UC.CONCLUSION:AFI has application in detecting inflammatory lesions,including microscopic activity in the co-lonic mucosa of UC patients,based on the green color component of images.

Fundus autofluorescence in central serous chorioretinopathy: association with spectral-domain optical coherence tomography and fluorescein angiography

and FA for identifying pathological abnormalities in CSC. The characteristics of IA AF in CSC were attributable to the modification of melanin in the RPE. IR- AIM: To evaluate the correlation among changes in fundus autofluorescence (AF) measured using infrared fundus AF (IR -AF) and short-wave length fundus AF (SW -AF) with changes in spectral -domain optical coherence tomography (SD -OCT) and fluorescein angiography (FA) in central serous chorioretinopathy (CSC). METHODS: Two hundred and twenty consecutive patients with CSC were included. In addition to AF, patients were assessed by means of SD -OCT and FA. Abnormalities in images of IA -AF, SW -AF, FA were analyzed and correlated with the corresponding outer retinal alterations in SD-OCT findings. RESULTS: Eyes with abnormalities on either IR-AF or SW-AF were found in 256 eyes (58.18%), among them 256 eyes (100%) showed abnormal IR -AF, but SW-AF abnormalities were present only in 213 eyes (83.20%). The hypo-IR-AF corresponded to accumulation of subretinal liquid, collapse of retinal pigment epithelium (APE) or detachment of APE with or without RPE leakage point in the corresponding area. The hyper -IR -AF corresponded to the area with loss of the ellipsoid portion of the inner segments and sub -sensory retinal deposits or focal melanogenesis under sensory retina. The hypo-SW-AF corresponded to accumulation of subretinal liquid or atrophy of RPE. The hyper -SW -AF associated with sub -sensory retinal deposits, detachment of RPE and focal melanogenesis. CONCLUSION: IR-AF was more sensitive than SW-AF AF should be used as a common diagnostic tool for identifying pathological lesion in CSC.

Autofluorescence imaging and magnification endoscopy

It is well known that angiogenesis is critical in the transition from premalignant to malignant lesions.Consequently,early detection and diagnosis based on morphological changes to the microvessels are crucial.In the last few years,new imaging techniques which utilize the properties of light-tissue interaction have been developed to increase early diagnosis of gastrointestinal(GI) tract neoplasia.We analyzed several "red-flag" endoscopic techniques used to enhance visualization of the vascular pattern of preneoplastic and neoplastic lesions(e.g.trimodal imaging including autofluorescence imaging,magnifying endoscopy and narrow band imaging).These new endoscopic techniques provide better visualization of mucosal microsurface structure and microvascular architecture and may enhance the diagnosis and characterization of mucosal lesions in the GI tract.In the near future,it is expected that trimodal imaging endoscopy will be practiced as a standard endoscopy technique as it is quick,safe and accurate for making a precise diagnosis of gastrointestinal pathology,with an emphasis on the diagnosis of early GI tract cancers.Further large-scale randomized controlled trials comparing these modalities in different patient subpopulations are warranted before their endorsement in the routine practice of GI endoscopy.

Advanced endoscopic imaging in Barrett's oesophagus:A review on current practice

Over the last few years,improvements in endoscopic imaging technology have enabled identification of dysplasia and early cancer in Barrett's oesophagus.New techniques should exhibit high sensitivities and specificities and have good interobserver agreement.They should also be affordable and easily applicable to the community gastroenterologist.Ideally,these modalities must exhibit the capability of imaging wide areas in real time whilst enabling the endoscopist to specifically target abnormal areas.This review will specifically focus on some of the novel endoscopic imaging modalities currently available in routine practice which includes chromoendoscopy,autofluorescence imaging and narrow band imaging.

Role of wide-field autofluorescence imaging and scanning laser ophthalmoscopy in differentiation of choroidal pigmented lesions

·AIM:Toevaluatethe diagnostic properties of wide-field fundus autofluorescence(FAF) scanning laser ophthalmoscope(SLO) imaging for differentiating choroidal pigmented lesions.·METHODS: A consecutive series of 139 patients were included, 101 had established choroidal melanoma with13 untreated lesions and 98 treated with radiotherapy.Thirty-eight had choroidal nevi. All patients underwent a full ophthalmological examination, undilated wide-field imaging, FAF and standardized US examination. FAF images and imaging characteristics from SLO were correlated with the structural findings in the two patient groups.·RESULTS: Mean FAF intensity of melanomas was significantly lower than the FAF of choroidal nevi. Only 1out of 38 included eyes with nevi touched the optic disc compared to 31 out of 101 eyes with melanomas. In 18 out of 101 melanomas subretinal fluid was seen at the pigmented lesion compared to none seen in eyes with confirmed choroidal nevi. In 'green laser separation', a trend towards more mixed FAF appearance of melanomas compared to nevi was observed. The mean maximal and minimal transverse and longitudinal diameters of melanomas were significantly higher than those of nevi.·CONCLUSION: Wide-field SLO and FAF imaging may be an appropriate non-invasive diagnostic screening tool to differentiate benign from malign pigmented choroidal lesions.

Comparison of autofluorescence and optical coherence tomography findings in acute and chronic central serous chorioretinopathy

AIM:To discuss and compare the fundus autofluorescence(FAF)and optical coherence tomography(OCT)in acute or chronic central serous chorioretinopathy(CSCR).METHODS:Medical records of 100 cases of CSCR were reviewed.Acute and chronic cases were evaluated according to the duration of decreased visual acuity,serous retinal detachment(RD)and focal leakage on fluorescein angiography(FA).Chi-square test was used for statistical analysis.RESULTS:Forty cases had acute and 60 cases had chronic CSCR.FAF showed focal hypo-autofluorescence in 34(85%)and iso-autofluorescence in 6(15%)of acute cases and hypo-autofluorescence in 51(85%),hyperautofluorescence in 6(10%)and iso-autofluorescence in3(5%)of chronic cases.OCT showed serous RD with distinct borders correlated with FAF findings(hypoautofluorescence)in all acute CSCR cases.In chronic CSCR group,OCT showed serous RD with indistinct borders correlated with FAF findings.The differences between the OCT and FAF findings of the two groups were significant(P=0.000).CONCLUSION:OCT and FAF findings can support the clinical observations in differential diagnosis of acute and chronic CSCR and help clinicians to evaluate retinal pigment epithelium,outer segments of photoreceptors and the components of serous RD.

Infrared autofluorescence, short-wave autofluorescence and spectral-domain optical coherence tomography of optic disk melanocytomas

AIM： To investigate the findings of infrared fundus autofluorescence（IR-AF） and spectral-domain optical coherence tomography（SD-OCT） in eyes with optic disc melanocytoma（ODM）.· METHODS： IR-AF findings and those of other ophthalmologic imaging examinations, including short-wave autofluorescence（SW-AF）, fluorescein angiography（FA）, fundus color photography, and SD-OCT of 8 eyes of 8 consecutive cases with ODM were assessed.·RESULTS： The ODMs in all cases（100%） presented similar IR-AF, SW-AF, and FA findings. On IR-AF images, ODMs showed outstanding hyper-AF with well-defined outline. On SW-AF images, the area of ODMs presented as hypo-AF. FA images revealed the leaking retinal telangiectasia on the surface of the ODMs. On SDOCT images in 8 cases（100%）, the ODMs were sloped with highly reflective surface, which were disorganized retina and optic nerve layers. In 7 cases（87.5%）, peripapillary choroids were involved. The melanocytomas of 8 cases（100%） presented as optically empty spaces. Vitreous seeds were found in one case（12.5%）.· CONCLUSION： IR-AF imaging may provide a new modality to evaluate the pathologic features of ODMs,and together with SW-AF imaging, offers a new tool to study biological characteristics associated with ODMs.SD-OCT is a valuable tool in delimitating the tumor extension and providing morphological information about the adjacent retinal tissue.

Image-enhanced endoscopy for diagnosis of colorectal tumors in view of endoscopic treatment

Recently,image-enhanced endoscopy(IEE) has been used to diagnose gastrointestinal tumors.This method is a change from conventional white-light(WL) endoscopy without dyeing solution,requiring only the push of a button.In IEE,there are many advantages in diagnosis of neoplastic tumors,evaluation of invasion depth for cancerous lesions,and detection of neoplastic lesions.In narrow band imaging(NBI) systems(Olympus Medical Co.,Tokyo,Japan),optical filters that allow narrow-band light to pass at wavelengths of 415 and 540 nm are used.Mucosal surface blood vessels are seen most clearly at 415 nm,which is the wavelength that corresponds to the hemoglobin absorption band,while vessels in the deep layer of the mucosa can be detected at 540 nm.Thus,NBI also can detect pit-like structures named surface pattern.The flexible spectral imaging color enhancement(FICE) system(Fujifilm Medical Co.,Tokyo,Japan) is also an IEE but different to NBI.FICE depends on the use of spectral-estimation technology to reconstruct images at different wavelengths based on WL images.FICE can enhance vascular and surface patterns.The autofluorescence imaging(AFI) video endoscope system(Olympus Medical Co.,Tokyo,Japan) is a new illumination method that uses the difference in intensity of autofluorescence between the normal area and neoplastic lesions.AFI light comprises a blue light for emitting and a green light for hemoglobin absorption.The aim of this review is to highlight the efficacy of IEE for diagnosis of colorectal tumors for endoscopic treatment.

No DCX-positive neurogenesis in the cerebral cortex of the adult primate

Whether endogenous neurogenesis occurs in the adult cortex remains controversial.An increasing number of reports suggest that doublecortin(DCX)-positive neurogenesis persists in the adult primate cortex,attracting enormous attention worldwide.In this study,different DCX antibodies were used together with NeuN antibodies in immunohistochemistry and western blot assays using adjacent cortical sections from adult monkeys.Antibody adsorption,antigen binding,primary antibody omission and antibody-free experiments were used to assess specificity of the signals.We found either strong fluorescent signals,medium-weak intensity signals in some cells,weak signals in a few perikarya or near complete lack of labeling in adjacent cortical sections incubated with the various DCX antibodies.The putative DCX-positive cells in the cortex were also positive for NeuN,a specific marker of mature neurons.However,further experiments showed that most of these signals were either the result of antibody cross reactivity,the non-specificity of secondary antibodies or tissue autofluorescence.No confirmed DCX-positive cells were detected in the adult macaque cortex by immunofluorescence.Our findings show that DCX-positive neurogenesis does not occur in the cerebral cortex of adult primates,and that false-positive signals(artefacts)are caused by antibody cross reactivity and autofluorescence.The experimental protocols were approved by the Institutional Animal Care and Use Committee of the Institute of Neuroscience,Beijing,China(approval No.IACUC-AMMS-2014-501).

Spectral-domain optical coherence tomography finding in cytomegalovirus retinitis in AIDS patients

AIM:To observe the findings of spectral domain optical coherence tomography(SD-OCT)scan in cytomegalovirus retinitis(CMVR).METHODS:Forty-six eyes of 33 patients with acquired immunodeficiency syndrome and CMVR were enrolled in the study.Complete ophthalmologic examinations,color fundus photography,SD-OCT and fundus autofluorescence(FAF)were performed for all patients at the first visit and each follow-up visit.Retinal necrosis in CMVR was analyzed on SD-OCT and classified into two types,the typical type and the atypical type.RESULTS:Forty-one eyes of active CMVR and 4 eyes of recurrent CMVR were classified into typical type,and 4 eyes with graying retinal lesion without hemorrhage or only punctate hemorrhage were classified into atypical type.In active stage of CMVR,the retina in typical type was significant thickened with hyperreflective lesion and full­thickness disruption of retinal architecture with enlarged vessel;while in atypical type,the retina was also destroyed in all layers but without thickening or slightly thinned.The choroid,vitreous and retinal vessels were not significantly involved.In healed stage,the retina was thin with destroyed layers in both types.In typical type,FAF showed mottled hypofluorescence mixed with punctuate hyperfluorescence.In atypical type,the retina showed some"cavity"in outer nuclear layer,and FAF showed mild hyperfluorescence.CONCLUSION:SD-OCT show different changes in the retina in typical type and atypical type of CMVR,which should be useful in assisting diagnosis and follow-up management of the disease.

Fundus autofluorescence imaging of patients with idiopathic macular hole

AIM:To investigate the role of fundus autofluo rescence(FAF) both in the diagnosis and the preoperative and postoperative evaluation of patients with idiopathic macular hole(MH).METHODS:Forty eyes of 40 patients diagnosed as idiopathic MH between May 2010 and May 2011 were included in this retrospective study.All patients underwent full ophthalmologic examinations and imagings including fluorescein angiography,fundus autofluorescence(FAF) and optical coherence tomography.Thirty of these patients underwent MH surgery.FAF findings were associated with duration of symptoms,visual acuity at presentation,stage of MH,and postoperative anatomical correction.RESULTS:The mean duration of patients’ symptoms was 3.8±2.0(1-9) months.The MH was stage 2 in 4(10%),stage 3 in 24(60%) and stage 4 in 12(30%) eyes.The median preoperative best corrected visual acuity was 20/200(between 20/800 and 20/100).Twenty-eight of cases(70%) showed a stellate appearance with dark radiating striae.Having a visual acuity ≥20/200 was significantly more common in eyes with stellate appearance(P【0.001).The mean duration of symptoms was significantly shorter in eyes with stellate appearance(2.75±0.8 vs 6.33±1.61 months)(P【0.001).The frequency of stage 4 MH was significantly higher in eyes with nonstellate appearance(P【0.001).Anatomical correction of MH was achieved in 91.3%(21/23) of eyes with stellate appearance and 71.4%(5/7) of eyes without this appearance(P=0.225).CONCLUSION:Stellate appearance in FAF is associated with earlier stages of macular hole,better visual acuity at presentation,shorter duration of symptoms,thus more favorable prognosis.

Detection accuracy for epithelial dysplasia using an objective autofluorescence visualization method based on the luminance ratio

The autofluorescence visualization method （AVM） uses blue excitation light to assist in the diagnosis of epithelial dysplasia. It detects epithelial dysplasia as a black area, which is known as fluorescence visualization loss （FVL）. In this study, we evaluated the detection accuracy for epithelial dysplasia of the tongue using the objective AVM and assessed its possible clinical utility. Seventy-nine tongue specimens clinically suspected to have leukoplakia or squamous cell carcinoma （SCC） were analyzed. First, the AVM was subjectively performed using the Visually Enhanced Lesion scope （VELscope）, and the iodine-staining method was then performed. After biopsy, the histopathological results and the luminance ratio between the lesion and healthy tissue were compared, and a receiver operating characteristic curve was created. The cutoff value for the objective AVM was determined; the lesion was considered FVL-positive or -negative when the luminance ratio was higher or lower than the cutoff value, respectively. The histopathological diagnoses among the 79 specimens were SCC （n = 30）, leukoplakia with dysplasia （n = 34）, and leukoplakia without dysplasia （n= 15）. The cutoff value of the luminance ratio was 1.62, resulting in 66 FVL-positive and 13 FVL-negative specimens. The luminance ratio was significantly higher in the epithelial dysplasia-positive than -negative group （P〈O.O00 1）. The objective AVM showed much higher consistency between histopathological results than did the two methods （kappa statistic = 0.656）. In conclusion, objective autofluorescence visualization has a potential as an auxiliary method for diagnosis of epithelial dysplasia.

New aspects of modern endoscopy

The prognosis for patients with malignancies of the ga-strointestinal-tract is strictly dependent on early detec-tion of premalignant and malignant lesions. However, small, flat or depressed neoplastic lesions remain dif-ficult to detect with these technologies thereby limiting their value for polyp and cancer screening. At the same time computer and chip technologies have undergone major technological changes which have greatly im-proved endoscopic diagnostic investigation. New imag-ing modalities and techniques are very notable aspects of modern endoscopy. Chromoendoscopy or filter-aided colonoscopy(virtual chromoendoscopy) with high defi-nition endoscopes is able to enhance the detection and characterization of lesions. Finally, confocal laser en-domicroscopy provides histological confirmation of the presence of neoplastic changes. The developing tech-niques around colonoscopy such as the retro-viewing colonoscope, the balloon-colonoscope or the 330-de-grees-viewing colonoscope try to enhance the efficacy by reducing the adenoma miss rate in right-sided, non-polypoid lesions. Colon capsule endoscopy is limited to identifying cancer and not necessarily small adenomas. Preliminary attempts have been made to introduce this technique in clinical routine.

Era of Barrett’s surveillance: Does equipment matter?

Barrett’s esophagus is a consequence of long standing gastro-esophageal reflux disease and predisposes to the development of esophageal adenocarcinoma. Regular surveillance endoscopies can detect curable early neoplasia in asymptomatic patients, which in turn could improve the prognosis compared to symptomatic cancer. Early neoplastic lesions, which are amenable for local therapy, could be treated endoscopically, avoiding a major surgery. However, in the absence of obvious mucosal lesions, random four quadrant biopsies are done, which is associated with significant sampling error. Newer imaging modalities, such as autofluorescence endoscopy, are helpful in detecting subtle lesions that could be examined in detail with narrow band imaging to characterize and target biopsies. This has the potential benefit of reducing the number of random biopsies with a better yield of dysplasia. Confocal endomicroscopy provides "optical biopsies" and is a valuable tool in targeting biopsies to improve dysplasia detection; however, this is technically challenging. Fuji intelligent chromoendoscopy and I-Scan are recent additions to the imaging armamentarium that have produced notable early results. While all these additional new imaging techniques are promising, a thorough examination by high resolution white light endoscopy after clearing the mucosa with mucolytics should be the minimum standard to improve dysplasia detection during Barrett’s surveillance.

Surveillance using trimodal imaging endoscopy after endoscopic submucosal dissection for superficial gastric neoplasia

AIM: To evaluate the effectiveness of trimodal imaging endoscopy (TME) to detect another lesion after endoscopic submucosal dissection (ESD) for superficial gastric neoplasia (SGN).

Long term follow-up of a family with GUCY2D dominant cone dystrophy

AIM: To describe long term follow-up in a family with GUCY2D dominant cone dystrophy. METHODS: Optical coherence tomography scans and fundus autofluorescence images were obtained. Flash and pattern electroretinograms(ERGs) and occipital pattern reversal visual evoked potentials were recorded. RESULTS: Two members of the same family(father and son) were identified to have the heterozygous R838 C mutation in the GUCY2D gene. The father presented at the age of 45 with bilateral bull’s eye maculopathy and temporal disc pallor. Over 13 y of serial follow up visits, the bull’s eye maculopathy progressed gradually into macular atrophy. Electrophysiological tests were significantly degraded suggesting poor macular function. Spectraldomain optical coherence tomography(SD-OCT) scans showed progressive loss and disruption of the ellipsoid layer at the foveal level. His son presented at the age of 16 with bilateral granular retinal pigment epithelial changes in both maculae. Electrophysiological testing was initially borderline normal but has gradually deteriorated to show reduced cone ERGs and macula function. SD-OCT demonstrated gradual macular thinning and atrophy bilaterally. Unlike his father, there was no disruption of the ellipsoid layer.CONCLUSION: Both family members exhibited gradual changes in their fundi, electrophysiological testing and multimodal imaging. Changes were milder than those observed in other mutations of the same gene.

Autofluorescence imaging endoscopy can distinguish non-erosive reflux disease from functional heartburn: A pilot study

AIM: To investigate whether autofluorescence imaging (AFI) endoscopy can distinguish non-erosive reflux disease (NERD) from functional heartburn (FH).METHODS: In this prospective observational trial, 127 patients presenting with typical reflux symptoms for &#x0003e; 6 mo were screened. All the participants underwent endoscopy, during which white light imaging (WLI) was followed by AFI. Finally 84 patients with normal esophageal appearance on WLI were enrolled. It was defined as being suggestive of NERD if one or more longitudinal purple lines longer than one centimeter were visualized in the distal part of the esophagus during AFI endoscopy. Ambulatory 24-h multichannel intraluminal impedance and pH monitoring was also performed. After standard proton-pump inhibitor (PPI) tests, subjects were divided into an NERD group and an FH group and the diagnostic performance of AFI endoscopy to differentiate NERD from FH was evaluated.RESULTS: Of 84 endoscopy-negative patients, 36 (42.9%) had a normal pH/impedance test. Of these, 26 patients with favorable responses to PPI tests were classified as having NERD. Finally 10 patients were diagnosed with FH and the others with NERD. Altogether, 68 (81.0%) of the 84 patients were positive on AFI endoscopy. In the NERD group, there were 67 (90.5%) patients with abnormal esophageal findings on AFI endoscopy while only 1 (10%) patient was positive on AFI endoscopy in the FH group. The sensitivity and specificity of AFI in differentiating NERD from FH were 90.5% (95%CI: 81.5%-96.1%) and 90.0% (95%CI: 55.5%-99.7%), respectively. Meanwhile, the accuracy, positive predictive value and negative predictive value of AFI in differentiating between NERD and FH were 90.5% (95%CI: 84.2%-96.8%), 98.5% (95%CI: 92.1%-99.9%) and 56.3% (95%CI: 30.0%-80.2%), respectively.CONCLUSION: Autofluorescence imaging may serve as a complementary method in evaluating patients with NERD and FH.