Characteristics of late negative ERG responses elicited by sawtooth flicker.

BACKGROUND: This study aimed to determine whether the properties of the late negative responses (LNRs) of the electroretinogram (ERG) elicited by sawtooth flicker are consistent with the characteristics of the photopic negative response generated by a light pulse (PhNRpulse). METHODS: ERG recordings were obtained from 10 visually normal individuals and from 6 patients with optic atrophy (OA) in response to 8-Hz rapid-on and rapid-off sawtooth flicker and to brief (4 ms) light pulses. All stimuli were either long wavelength (R), middle wavelength (G), or a combination of equal luminances of long and middle wavelengths (Y) presented on a short-wavelength, rod-saturating adapting field. Amplitudes of LNRs were obtained in response to rapid-on (LNRon) and rapid-off (LNRoff) sawtooth flicker and were also derived from the sum of the ERG waveforms to the two sawtooth phases (LNRadd). RESULTS: For the control subjects, PhNRpulse amplitude varied with stimulus wavelength, being largest in response to a long-wavelength pulse, as expected. However, the amplitudes of LNRon, LNRoff, and LNRadd were not significantly different for R, Y, and G sawtooth flicker. Despite the absence of a chromatic effect, LNRoff and LNRadd amplitudes were significantly smaller in the OA patients than in the controls, similar to the results for the PhNRpulse, implying an inner retinal origin for the LNRoff and LNRadd. However, LNRon amplitudes did not differ significantly between the OA patients and controls, although there was a significant correlation between the LNRon and PhNRpulse for R stimuli. CONCLUSION: We conclude that LNRoff and LNRadd but not LNRon can be useful measures to assess the integrity of the inner retina that can complement the PhNRpulse.

Xerophthalmia and acquired night blindness in a patient with a history of gastrointestinal neoplasia and normal serum vitamin A levels.

A 69-year-old male patient presented to our department with a 3-month history of nyctalopia. Reviewing of his general health revealed a history of gastrointestinal tumor treated with a modified WHIPPLE operation. Ocular findings at presentation included mild xerophthalmic features and nonspecific pigmentary retinal changes. A standard full-field electroretinogram (ERG) was obtained that showed normal photopic function and extinguished scotopic function. The ocular symptoms, the history and the ERG findings suggested vitamin A deficiency as a possible cause for his complaints. Serum vitamin A levels were subsequently requested, but the results were within normal limits. Despite the normal serum vitamin A levels, the patient was instructed to commence treatment with high doses of oral vitamin A supplements. One month after the onset of the treatment, the patient reported that his visual function has significantly improved, while repeat ERG testing revealed that scotopic function has improved to normal levels. This case highlights that in patients with acquired night blindness due to vitamin A deficiency, the ERG responses possibly represent a more sensitive marker compared to the serum levels of vitamin A.

Intravenous rituximab and oral cyclophosphamide for the treatment of cancer­associated retinopathy in a patient with epithelial ovarian cancer: A case report.

Cancer-associated retinopathy (CAR) is a rare paraneoplastic disorder mediated by auto-antibodies that cross-react with retinal antigens leading to gradual visual defects. Early diagnosis and initiation of treatment is crucial to avoid permanent visual loss. Although most patients with CAR respond to intravenous steroids and intravenous immunoglobulin (IVIG), there are some cases refractory to the aforementioned treatment strategies. The present study describes a case of CAR in a patient with ovarian cancer that was initially resistant to most treatment regimens (chemotherapy, steroids, IVIG). Treatment with rituximab at 375 mg/m2 and oral cyclophosphamide was administered and the patient showed marked improvement of visual acuity. Electroretinogram showed a 40 and 10% improvement in scotopic and photopic vision, respectively. Notably, at the most recent follow up, the patient was still in remission. In conclusion, treatment with intravenous rituximab and oral cyclophosphamide is a promising treatment option for those cases of CAR that do not respond to steroids, immunomodulatory agents and IVIG.

Evaluation of retinal nerve fiber layer thickness in patients with retinitis pigmentosa using spectral-domain optical coherence tomography.

PURPOSE: To measure the peripapillary retinal nerve fiber layer (RNFL) thickness using spectral-domain optical coherence tomography in patients with retinitis pigmentosa. METHODS: Fifty eyes of 30 patients with retinitis pigmentosa underwent a complete ocular examination, including best-corrected visual acuity using a Snellen chart, slit-lamp biomicroscopic examination, and Goldmann applanation intraocular pressure measurement. Dilated fundus examination was performed using both direct and indirect ophthalmoscopy. In addition, all patients underwent peripapillary RNFL thickness measurements using an OPKO spectral-domain optical coherence tomography (OPKO Instrumentations, Miami, FL). RESULTS: The mean (± SD) age of the study cohort was 45.8 (± 16.3) years. Of the 50 eyes, 18 (36%) showed a thinning of the peripapillary RNFL in 1 or more quadrants and 21 (42%) showed a thickening of the peripapillary RNFL in 1 or more quadrants. Four eyes (8%) showed both thinning and thickening of the peripapillary RNFL thickness. The overall circumferential RNFL thickness of the 14 eyes that showed only thinning in at least 1 quadrant was 78.78 µm. For the 17 eyes that showed only thickening in at least 1 quadrant, the RNFL thickness was 119.69 µm. The values of the eyes with thinning and the eyes with thickening were significantly different from normal (t = 6.31 and P < 0.01 for thickening; t = 3.62 and P < 0.01 for thinning). CONCLUSION: Using spectral-domain optical coherence tomography testing, we demonstrated in the current study that the peripapillary RNFL thickness in patients with RP can be decreased, increased, or maintained within normal limits. Assessment of the RNFL thickness seems prudent in these patients, particularly for identifying notable degrees of RNFL thinning in those being considered for future therapeutic trials.

Cancer-associated retinopathy presenting as retinal vasculitis with a negative ERG suggestive of on-bipolar cell pathway dysfunction.

A 62-year-old female patient presented to our clinic complaining of a 2 month history of shimmering photopsias and floaters. An ocular examination, fluorescein angiography, and electrophysiological testing were obtained that suggested either an inflammatory retinal vasculitis or a paraneoplastic syndrome. Melanoma-associated retinopathy was highly suspected despite the absence of previous history for cutaneous melanoma since an electronegative scotopic ERG was recorded on standard flash electroretinography. Additional investigations revealed the presence of a primary breast tumor with secondary lung and pancreatic metastasis that led to the diagnosis of cancer-associated retinopathy. The patient received chemotherapy and 4 months after the initial presentation her visual complaints but also her retinal function showed marked improvement. Cancer-associated retinopathy needs to be considered in patients presenting with retinal vasculitis and electrophysiological testing can tailor the approach in these cases.

Visual acuity loss in recessive retinitis pigmentosa and its correlation with macular lesions.

PURPOSE: To determine the visual acuity loss in patients with autosomal recessive retinitis pigmentosa and its relation to the presence of macular lesions. METHODS: A total of 145 patients were included in the visual acuity analysis, and 139 patients were included in the analysis of their macular status. Patients with a history of parental consanguinity or an affected sister and parents unaffected with retinitis pigmentosa were considered as having an autosomal recessive mode of inheritance. RESULTS: Regardless of age, 68 patients (47%) had visual acuity of 20/40 or better, 109 (75%) had better than 20/200 in at least 1 eye, and 36 (25%) had an acuity of 20/200 or worse in both eyes. An evaluation of the macular status demonstrated that 55 patients (39.6%) had no macular lesion and 77 (55.4%) had an atrophic lesion (either bull's-eye or geographic). Seventy-five percent of patients with no macular lesion had a visual acuity of 20/40 or better and 34 patients (44%) with an atrophic lesion had a visual acuity better than 20/70. CONCLUSION: These data can be useful to counsel patients on the potential visual acuity impairment likely to be observed at different ages and identify the association of visual acuity loss with macular changes.

Infrared scanning laser ophthalmoscope imaging of the macula and its correlation with functional loss and structural changes in patients with stargardt disease.

PURPOSE: To correlate the degree of functional loss with structural changes in patients with Stargardt disease. METHODS: Eighteen eyes of 10 patients with Stargardt disease were studied. Scanning laser ophthalmoscope infrared images were compared with corresponding spectral-domain optical coherence tomography scans. Additionally, scanning laser ophthalmoscope microperimetry was performed, and results were superimposed on scanning laser ophthalmoscope infrared images and in selected cases on fundus autofluorescence images. RESULTS: Seventeen of 18 eyes showed a distinct hyporeflective foveal and/or perifoveal area with distinct borders on scanning laser ophthalmoscope infrared images, which was less evident on funduscopy and incompletely depicted in fundus autofluorescence images. This hyporeflective zone corresponded to areas of significantly elevated psychophysical thresholds on microperimetry testing, in addition to thinning of the retinal pigment epithelium and disorganization or loss of the photoreceptor cell inner segment-outer segment junction and external-limiting membrane on spectral-domain optical coherence tomography. CONCLUSION: Scanning laser ophthalmoscope infrared fundus images are useful for depicting retinal structural changes in patients with Stargardt disease. A spectral-domain optical coherence tomography/scanning laser ophthalmoscope microperimetry device allows for a direct correlation of structural abnormalities with functional defects that will likely be applicable for the determination of retinal areas for potential improvement of retinal function in these patients during future clinical trials and for the monitoring of the diseases' natural history.

Macular vitelliform lesion in desferrioxamine-related retinopathy.

To report a case of a macular vitelliform lesion associated with desferrioxamine treatment. Ocular, electrophysiological, psychophysical, perimetric, fluorescein angiographic, fundus autofluorescence, and spectral-domain OCT examinations were obtained on a 45-year-old Caucasian woman with thalassemia major treated with blood transfusions and desferrioxamine. The patient was observed to have a vitelliform macular lesion in the right eye with a hypopigmented macular lesion and retinal pigment mottling in the left. At the most recent follow-up visit, best-corrected visual acuity was 20/70 in the right eye and 20/25 in left. Full-field electroretinogram (ERG) testing showed normal cone and rod responses. Mild localized elevations of rod psychophysical thresholds were found. A vitelliform macular lesion can develop in patients treated with desferrioxamine. Some such patients may not show diffuse photoreceptor cell functional loss as determined by electrophysiological testing.

Corrigendum to "Mutation Spectrum of the ABCA4 Gene in a Greek Cohort with Stargardt Disease: Identification of Novel Mutations and Evidence of Three Prevalent Mutated Alleles".

[This corrects the article DOI: 10.1155/2018/5706142.].

Long-term follow-up of Intacs in keratoconus.

PURPOSE: To evaluate long-term follow-up of Intacs microthin prescription inserts (Addition Technology, Inc, Fremont, California, USA) for the management of keratoconus. DESIGN: A long-term (five years) retrospective, follow-up study. METHODS: Seventeen eyes of 15 patients with keratoconus ages 24 to 52 years (mean age +/- standard deviation [SD], 34.0 +/- 10.5 years) who had completed five years of follow-up (mean follow-up +/- SD, 67.2 +/- 7.5 months; range, 58 to 78 months) were included. Two Intacs segments of 0.45-mm thickness were inserted in the cornea of each eye, aiming at embracing the keratoconus area to try to achieve maximal flattening. RESULTS: No late postoperative complications occurred in this series of patients. At five years, the spherical equivalent error was statistically significantly reduced (pre-Intacs, mean +/- SD -5.54 +/- 5.02 diopters [D]; range, -12.50 to 3.63 D; -3.02 +/- 2.65 D; range, -8.25 to 1.88 D) (P = .01). Pre-Intacs uncorrected visual acuity (UCVA) was 20/50 or worse in all eyes (range, counting fingers to 20/50), whereas, at the last follow-up examination, 10 (59%) of 17 eyes had UCVA of 20/50 or better (range, counting fingers to 20/32). Six eyes (35%) maintained the pre-Intacs best spectacle-corrected visual acuity (BSCVA) and one eye lost 3 lines of BSCVA, whereas the rest of the 10 eyes (59%) experienced a gain of one up to 8 lines. CONCLUSIONS: After five years, intracorneal ring segments implantation improved UCVA, BSCVA, and refraction in the majority of the keratoconus patients. There was no evidence of progressive sight-threatening complications in this study.

The use of intravitreal etanercept in diabetic macular oedema.

The aim of this pilot study was to investigate the effect of intravitreal administration of etanercept in refractory diabetic macular edema. Seven patients diagnosed with diabetic macular edema, refractory to previous treatment, were enrolled. They all received 2 consecutive intravitreal injections of 2.5 mg (0, 1 ml) of Etanercept (Enbrel), with a two-week interval. In all patients visual acuity assessment, fundoscopy and fluorescein angiography were performed prior to the first injection, weekly for the first month, as well as 2 and 3 months following the first injection. No adverse reactions or adverse events were noticed in any patient. Analysis of the data indicates a trend for improvement of visual acuity, a slight worsening of hard exudates and fluorescein leakage, while hemorrhages remained stable, 3 months after initiation of therapy. However, no statistical significance has been reached. This small pilot study did not reveal any improvement in the clinical course of patients with refractory diabetic macular edema after the intravitreal injection of etanercept. Further research is warranted in order to obtain conclusive results concerning the role of anti-TNF therapy in diabetic macular edema.

Spontaneous Regression of Choroidal Neovascularization in a Patient with Pattern Dystrophy.

Purpose. To present a case of a patient with pattern dystrophy (PD) associated choroidal neovascularization (CNV) that resolved spontaneously without treatment. Methods. A 69-year-old male patient was referred to our unit, for evaluation of a recent visual loss (metamorphopsias) in his left eye. Fundus examination, fundus autofluorescence imaging, and fluorescein angiography showed a choroidal neovascular membrane in his left eye. Since visual acuity was satisfactory the patient elected observation. Clinical examination and OCT testing were repeated at 6 and 12 months after presentation. Results. Visual acuity remained stable at the level of 0.9 (baseline BCVA) during the follow-up period (12 months). Repeat OCT testing showed complete spontaneous regression of the choroidal neovascular membrane without evidence of intra- or subretinal fluid in both follow-up visits. Conclusions. Spontaneous regression of choroidal neovascularization can occur in patients with retinal dystrophies and associated choroidal neovascular membranes. The decision to treat or observe these patients relies strongly on the presenting visual acuity, since, in isolated instances, spontaneous resolution of choroidal neovascularization may occur.

The effect of intravitreal anti-VEGF on the pigment epithelial detachment in eyes with the exudative type of age-related macular degeneration.

PURPOSE: To evaluate the effect of anti-VEGF treatment on pigment epithelial detachment (PED) secondary to the exudative type of age-related macular degeneration (AMD). METHODS: Retrospective analysis of 30 eyes (28 patients) with exudative AMD accompanied by PED (receiving anti-VEGF injections). Alterations of the PED morphology were qualitatively assessed with optical coherence tomography (OCT). Changes in best-corrected visual acuity (BCVA) and number of injections were compared to 30 control eyes (30 patients) exhibiting exudative AMD without PED. RESULTS: Mean follow-up was 19.8 months. Changes of the extent of PED were as follows: unchanged: 11 eyes (36.7%); reduced: 12 (40%); significantly reduced: 7 (23.3%). Mean paired difference in BCVA was -0.08 logMAR (p = 0.46) and in the number of injections was 2.1 injections (p = 0.04). CONCLUSIONS: A substantial number of the studied patients showed reduction of the extent of the PED after anti-VEGF treatment. The PED group required a higher number of injections.

Clinical and spectral-domain optical coherence tomography findings of patients with incomplete visual recovery after anatomically successful retinal detachment surgery.

Purpose. To identify causes of incomplete visual recovery in patients with anatomically successful retinal detachment surgery. Methods. This was a retrospective study of 61 eyes of 61 patients with at least 12-month follow-up and complete preoperative, intraoperative, and postoperative record. Postoperative visual acuity (VA) more than 0.18 logMAR was considered as incomplete visual recovery. Complete ophthalmic examination and Spectral-Domain OCT (SD-OCT) imaging were performed at last follow-up. Results. Twenty-nine eyes (47.5%) had a postoperative VA < 0.18 logMAR and 32 eyes (52.5%) had a postoperative VA ≥ 0.18 logMAR. Mean follow-up was 32.8 ± 17.3 months. Incomplete visual recovery was strongly correlated with presence of macular pathology (P = 0.002), a detached macula preoperatively (P = 0.02), retinotomy (P = 0.025), and pars plana vitrectomy and use of silicon oil as a tamponade agent (P = 0.009). Also, although there was a strong correlation between ellipsoid zone disruption and incomplete visual recovery, a distinct, more course pathology could be identified in all cases of poor visual recovery related to edema, thickening, or atrophy of the macula. Conclusion. The careful postoperative evaluation of the macula using biomicroscopy and SD-OCT can help in diagnosis of alterations that can be associated with incomplete visual recovery.

Electroretinographic findings in a patient with congenital stationary night blindness due to a novel NYX mutation.

PURPOSE: To document a novel NYX gene mutation in a patient with X-linked complete congenital stationary night blindness and to describe this patient's electroretinogram (ERG) characteristics. METHODS: ERGs were recorded from a 17-year-old male with a previously unreported NYX mutation (819G > A) that results in a missense codon change (Trp237Ter). ERGs were recorded in response to brief-flash stimuli, 6.33-Hz sawtooth flicker, and sinusoidal flicker ranging from 6.33-100 Hz. The omitted stimulus response (OSR) of the flicker ERG, which is thought to be generated within the ON-pathway, was also assessed. RESULTS: The patient's single-flash responses were consistent with previously documented NYX ERG characteristics, including a high-luminance flash response that was electronegative under dark-adapted conditions and a square-like a-wave followed by an abnormally shaped positive potential under light-adapted conditions, both of which are consistent with an ON-pathway deficit. Further evidence for an ON-pathway deficit included: (1) ERGs to rapid-on sawtooth flicker in which b-wave amplitude was reduced more than a-wave amplitude, and (2) responses to sinusoidal flicker that lacked the normal amplitude minimum and phase inflection near 12 Hz, ERG characteristics that are like those of patients with other NYX mutations. Novel findings included a pronounced amplitude attenuation for sinusoidal flicker at frequencies above approximately 50 Hz and an absent OSR, suggesting ON-pathway dysfunction at high frequencies. CONCLUSION: The substantial loss of ERG amplitude and apparent ON-pathway dysfunction at high temporal frequencies distinguish this patient with a Trp237Ter NYX mutation from those with other previously reported NYX mutations.

Spectral-domain OCT peripapillary retinal nerve fibre layer thickness measurements in patients with Stargardt disease.

AIMS: To evaluate the presence of peripapillary retinal nerve fibre layer (RNFL) defects in patients with Stargardt disease by using spectral-domain optical coherence tomography (SD-OCT). METHODS: Fifty-two eyes of 27 patients with Stargardt disease underwent peripapillary RNFL thickness measurements using SD-OCT. RESULTS: Twenty-seven patients with Stargardt disease were enrolled. Their mean (±SD) age was 38.3 (14.7) years. Fourteen patients (51.9%) showed a thinning of the peripapillary RNFL in one or more quadrants in at least one eye, and four patients (14.8%) in both eyes. Five patients (18.5%) showed a thickening of the peripapillary RNFL in at least one eye, and four patients (14.8%) in both eyes. CONCLUSION: This study demonstrated the presence of defects in the peripapillary RNFL thickness in patients with Stargardt disease by using SD-OCT. It would be clinically prudent that Stargardt patients considered for various treatment options be considered for RNFL thickness measurements.

Structural and functional measures of inner retinal integrity following visual acuity improvement in a patient with hereditary motor and sensory neuropathy type VI.

PURPOSE: To report measures of inner retinal integrity following improvement in visual acuity and visual fields in a patient with hereditary motor and sensory neuropathy type VI (HMSN VI). CASE REPORT: The patient is a Caucasian male with HMSN VI (type 2A Charcot-Marie-Tooth disease and associated optic atrophy) and a c.1090C→T (p.R364W) mutation in the mitofusin 2 (MFN2) gene. The patient's best-corrected visual acuity improved from 20/200 (OD) and 20/400 (OS) at the initial visit to 20/25 in each eye when tested 7 years later. The visual field defects in both eyes that were present at the initial visit were absent at the follow-up visit. The structural integrity of the inner retina was assessed by an evaluation of retinal nerve fiber layer thickness (RNFLT) using optical coherence tomography (OCT), and the functional integrity was assessed by the amplitude of the photopic negative response (PhNR) of the electroretinogram (ERG). At the follow-up visit, the patient's RNFLT was less than the 5th percentile for control subjects in the superior and inferior quadrants OD and in one sector of the temporal quadrant OS, but was within normal limits elsewhere. The PhNR amplitude of each eye was below the lower limit of the normal range. CONCLUSION: The abnormally low PhNR amplitudes and abnormally thin RNFL in certain quadrants of the retina following improvement of visual acuity and visual fields to near-normal values illustrates the potential usefulness of assessing the structure and function of the inner retina in HMSN VI patients.

Structural and functional correlation in sickle cell retinopathy using spectral-domain optical coherence tomography and scanning laser ophthalmoscope microperimetry.

PURPOSE: To correlate macular structural changes by spectral-domain optical coherence tomography (SD-OCT) with functional changes by scanning laser ophthalmoscope (SLO) microperimetry testing in patients with sickle cell hemoglobinopathies. DESIGN: Prospective, investigational study. METHODS: Patients with electrophoretic confirmation of sickle cell hemoglobinopathies and normal subjects underwent SD-OCT and microperimetry testing with the OPKO Spectral OCT/SLO instrument. Based on SD-OCT findings, patients were grouped into those with focal macular thinning (Group A) and those without (Group B). Main outcome measure were mean retinal sensitivities measured by microperimetry and mean macular thicknesses in the 9 Early Treatment Diabetic Retinopathy Study (ETDRS)-like subfields. RESULTS: Thirty-seven eyes of 19 patients with sickle cell hemoglobinopathies (SS, SC, and S-thalassemia) and 34 eyes of 34 age-similar normal controls were included. Mean age and mean logMAR best-corrected visual acuity between Groups A and B were not statistically different (39.7 years vs 36.5 years, P = .64 and 0.015 vs 0.016, P = .93, respectively). Group A had significantly thinner retinas compared to Group B in the parafoveal superior (P = .019), parafoveal temporal (P < .004), parafoveal inferior (P = .003), perifoveal superior (P = .04), perifoveal temporal (P = .0005), and perifoveal inferior (P = .045) subfields. The overall mean microperimetry retinal sensitivities of Group A were significantly less than those of Group B (14.2 dB vs 16.5 dB, P = .00005). However, there was no statistical difference between Group B and controls (16.5 dB vs 16.7 dB, P = .63). CONCLUSION: Sickle cell patients with focal macular thinning present on SD-OCT have significantly decreased retinal sensitivities compared to those without focal thinning or normal controls based on mean microperimetry sensitivities, despite similar age and visual acuity. Microperimetry is a sensitive measurement of macular function in patients with sickle cell hemoglobinopathies.

Microperimetry and OCT findings in female carriers of choroideremia.

PURPOSE: To evaluate structural retinal changes and macular function by a combined spectral domain optical coherence tomography/scanning laser ophthalmoscope (OCT/SLO) microperimetry device in choroideremia carriers. METHODS AND MATERIALS: Ten choroideremia carriers were included in the study. All subjects had a complete ophthalmic examination in addition to Goldmann kinetic visual fields, OCT and microperimetry testing on a commercially available Spectral Domain (SD) OCT/SLO combination system. RESULTS: Microperimetry results demonstrated focal areas of threshold abnormalities in 50% of the subjects. OCT findings show subtle retinal pigment epithelium (RPE) irregularities with attenuation more pronounced outside the macular region. CONCLUSIONS: Long term follow up with microperimetric testing could be useful in monitoring any progressive loss of retinal function in choroideremia carriers.