Nicole Balducci

Swelling of the arcuate nerve fiber layer after internal limiting membrane peeling.

Purpose: The purpose of the study is to report the incidence of changes of the retinal nerve fiber layer in the early postoperative period after internal limiting membrane peeling for idiopathic macular hole and epiretinal membrane surgery. Methods: Interventional, noncomparative retrospective case series. Fifty-six eyes of 55 patients with an epiretinal membrane and 33 eyes of 31 patients with macular hole underwent pars plana vitrectomy and internal limiting membrane peeling. All patients received a complete ophthalmic examination, infrared and autofluorescence photography, and spectral-domain optical coherence tomography preoperatively and also at approximately 1 week, 1 month, and 3 months postoperatively. Vitrectomy and gas tamponade were performed with internal limiting membrane peeling after staining with Brilliant Peel. The main outcome measures were the presence of postoperative swelling of the arcuate retinal nerve fiber layer on spectral-domain optical coherence tomography, infrared and autofluorescence photographs, and its effect on best-corrected visual acuity. Results: On infrared and autofluorescence photographs, 28 (31.46%) of 89 eyes with internal limiting membrane peeling exhibited swelling of the arcuate retinal nerve fiber layer 1 week to 1 month postoperatively. Swelling of the arcuate retinal nerve fiber layer increased during the first month after surgery and resolved after a mean period of 2 months. These features were best visualized by autofluorescence imaging, as three to five dark striae originating from the optic nerve head, radiating in an arcuate pattern toward the macula. Simultaneous spectral-domain optical coherence tomography scanning through the striae indicated that they correspond to areas of focal swelling of the arcuate nerve fiber layer. No significant differences were found in eyes with or without swelling of the arcuate retinal nerve fiber layer for mean age or pre- and postoperative best-corrected visual acuity (P > 0.05). Conclusion: Swelling of the arcuate retinal nerve fiber layer often occurs after internal limiting membrane peeling for macular hole and epiretinal membrane. It is a transient feature after surgery that does not affect visual recovery. It is best visualized using infrared and autofluorescence imaging. Simultaneous infrared and spectral-domain optical coherence tomography imaging after macular surgery can detect transient inner retinal changes, which are not visible on clinical examination.

Endothelin-1 plasma levels and vascular endothelial dysfunction in primary open angle glaucoma.

AIMS To assess the relationship between endothelial dysfunction, endothelin 1 (ET-1) plasma levels and subclinical inflammation in primary open angle glaucoma (POAG) patients. MAIN METHODS We enrolled 40 POAG patients with progressive visual field damage, although well controlled intraocular pressure (IOP) and compared to age and sex matched healthxy subjects. Each patient underwent an ophthalmological examination, a standard achromatic perimetry (SAP), blood sampling to assess ET-1 plasma levels, an objective assessment of cellularity within the anterior chamber (FLARE) and measurement of flow mediated dilation (FMD) with high resolution 2-dimensional ultrasonographic imaging of the brachial artery. KEY FINDINGS At baseline, POAG patients, compared to healthy controls, showed an increase of ET-1 plasma levels: 2.83 ± 0.28 pg/ml vs. 1.75 ± 0.25 pg/ml (p<0.001), lower FMD values 4.46 ± 1.28% vs. 13.18 ± 2.80% (p<0.001) and increased FLARE values 9.98 ± 0.97 photons/ms vs. 5.87 ± 0.64 photons/ms (p<0.001). A follow up after 1 year revealed a further increase of ET-1 plasma levels (to 3.68 ± 0.60; p<0.001) and decrease of FMD (3.52 ± 1.28; p>0.001). SIGNIFICANCE The increase of ET-1 in POAG patients is related to vascular dysfunction (r=0.942; p=0.001) and vascular dysfunction is related to sub-clinical intraocular inflammation (r=0.968; p=0.001). Thus ET-1 and vascular dysfunction related to sub-clinical inflammation may play a key role in determining a progressive visual field damage in POAG patients who present a well-controlled IOP.

Retinal nerve fiber layer thickness modification after internal limiting membrane peeling.

Purpose: To identify early and late retinal nerve fiber layer thickness (RNFLT) modification after internal limiting membrane peeling for idiopathic macular hole or epiretinal membrane and to correlate RNFLT to visual field indices. Methods: Single-center, prospective, interventional consecutive case series. Complete ophthalmic examination, fundus images, and spectral domain optical coherence tomography were performed in 30 eyes of 30 patients before and 1, 3, and 6 months after surgery. Six peripapillary sectors (superotemporal, temporal, inferotemporal, inferonasal, nasal, superonasal) and global RNFLT were evaluated. Visual field was performed preoperatively and 6 months postoperatively. Results: Significant RNFLT modification was found after surgery (P < 0.0001). Specifically, RNFLT significantly increased in all, but the temporal sectors, 1 month after surgery, and it returned to preoperative values at the third month. Six months after surgery, RNFLT was lower than basal values in the superotemporal, inferotemporal, and temporal sectors (P < 0.001, P < 0.05, and P < 0.001, respectively) with an average reduction of 18.2 ± 9.8 µm. No correlation was found between RNFLT and the visual field indices. Conclusion: The diffuse RNFLT increase 1 month postoperatively could be because of inflammatory responses. The reduction of RNFLT in the temporal sectors 6 months postoperatively could indicate damage to the macular retinal nerve fiber layer caused by internal limiting membrane peeling.

Electrophysiological detection of delayed postretinal neural conduction in human amblyopia.

PURPOSE To evaluate macular function and neural conduction along postretinal visual pathways in amblyopic patients. METHODS Twenty-five anisometropic amblyopic patients (mean age, 7 ± 1.9 years; visual acuity [VA]: 0.44 ± 0.27 logMAR in amblyopic [AM] eyes and 0.023 ± 0.067 logMAR in sound [SE] eyes) and 25 age-similar control subject ([CE] eyes, VA of 0.0 ± 0.0 logMAR in both eyes) were enrolled. In AM, SE, and CE eyes, simultaneous pattern electroretinograms (PERGs) and visual evoked potentials (VEPs) were recorded in response to checks reversed at the rate of two reversals/second stimulating macular or extramacular areas (the check edge subtended 15 minutes and 60 minutes of visual arc, respectively). RESULTS Nonsignificant differences (ANOVA, P > 0.005) were observed in PERG, in VEP responses to the 60-minute stimulus, and in retinocortical time with the 60-minute stimulus (RCT; the difference between VEP P100 and PERG P50 implicit times) between AM, SE, and CE eyes. AM eyes showed a significant (P < 0.005) increase in VEP P100 implicit time and in RCT in response to the 15-minute stimulus, compared with the values observed in SE and CE eyes. In AM patients, the interocular difference in VA was significantly (Pearsons test, P < 0.005) related to the interocular difference VEP P100 latencies and RCT with the 15-minute stimulus. CONCLUSIONS Amblyopic eyes showed abnormal visual cortical responses only when the macular area was stimulated (increase in VEP P100 implicit times with the 15-minute stimulus). This functional impairment, in the presence of normal macular function (PERG responses similar to control eyes) may be attributable to a delay in postretinal neural conduction (increase in RCT).

Macular nerve fibre and ganglion cell layer changes in acute Leber's hereditary optic neuropathy

Aims To evaluate longitudinal retinal ganglion cell inner plexiform layer (GC-IPL) and macular retinal nerve fibre layer (mRNFL) thickness changes in acute Lebers hereditary optic neuropathy (LHON). Methods Six eyes of four patients with LHON underwent SD-OCT (optical coherence tomography) at month 1, 3, 6 and 12 after visual loss. In two eyes, the examination was carried out in the presymptomatic stage. The relationship and curves for area under the receiver operator characteristic (AUROC) were generated to assess the ability of each parameter to detect ganglion cell loss. Results Significant longitudinal thinning of GC-IPL and mRNFL was detected in LHON. GC-IPL thinning was detectable in the deviation map during the presymptomatic stage in the inner ring of the nasal sector and then it progressively extended following a centrifugal and spiral pattern. Similarly, mRNFL thinning began in the inferonasal sector and it progressively extended. No further statistically significant changes were detected after month 3. The highest level of AUROC values at 1 month were detected in the nasal sectors and inferonasal mRNFL thickness reached AUROC value=1. All the parameters were equally able to detect ganglion cell loss from month 2 to 12. Conclusions The natural history of GC-IPL thinning follows a specific pattern of reduction, reflecting the anatomical course of papillomacular fibres. Month 6 represents the end of GC-IPL loss. GC-IPL and mRNFL thinning is detectable before onset of visual loss. These observations can help future therapeutic approaches for both LHON carriers at high risk of conversion and patients with acute early LHON.

Unravelling the Complexity of Inherited Retinal Dystrophies Molecular Testing: Added Value of Targeted Next-Generation Sequencing

To assess the clinical utility of targeted Next-Generation Sequencing (NGS) for the diagnosis of Inherited Retinal Dystrophies (IRDs), a total of 109 subjects were enrolled in the study, including 88 IRD affected probands and 21 healthy relatives. Clinical diagnoses included Retinitis Pigmentosa (RP), Leber Congenital Amaurosis (LCA), Stargardt Disease (STGD), Best Macular Dystrophy (BMD), Usher Syndrome (USH), and other IRDs with undefined clinical diagnosis. Participants underwent a complete ophthalmologic examination followed by genetic counseling. A custom AmpliSeq™ panel of 72 IRD-related genes was designed for the analysis and tested using Ion semiconductor Next-Generation Sequencing (NGS). Potential disease-causing mutations were identified in 59.1% of probands, comprising mutations in 16 genes. The highest diagnostic yields were achieved for BMD, LCA, USH, and STGD patients, whereas RP confirmed its high genetic heterogeneity. Causative mutations were identified in 17.6% of probands with undefined diagnosis. Revision of the initial diagnosis was performed for 9.6% of genetically diagnosed patients. This study demonstrates that NGS represents a comprehensive cost-effective approach for IRDs molecular diagnosis. The identification of the genetic alterations underlying the phenotype enabled the clinicians to achieve a more accurate diagnosis. The results emphasize the importance of molecular diagnosis coupled with clinic information to unravel the extensive phenotypic heterogeneity of these diseases.

Efficacy of two-month treatment with Xiloial® eyedrops for discomfort from disposable soft contact lenses

Purpose: To evaluate the efficacy and tolerability of Xiloial® monodose eyedrops in the treatment of patients suffering from subjective symptoms of discomfort related to disposable soft contact lens (dSCL) wear. Methods: Fifteen (12 female, three male, medium age 39 ± 9 years) dSCL wearers were enrolled. Inclusion criteria were Ocular Surface Disease Index (ODSI) symptom questionnaire score >12, tear film break-up time (TFBUT) <10 sec, Schirmer test I >10 mm over five minutes, mild punctuate keratopathy, and conjunctival staining (Oxford grading ≤4). Monodose Xiloial eyedrops were administered three times daily for a two-month period. Patients were evaluated at enrollment, after three days of washout (baseline), and after one and two months of treatment, by OSDI score, Schirmer test I, TFBUT, ferning test, ocular surface damage (Oxford grade), and serum albumin in tears (index of passive exudation related to serum leakage). Results: At endpoint versus baseline, respectively, the mean ± standard deviation of all variables improved as follows: OSDI (8.5 ± 3 versus 20.2 ± 1.6); TFBUT (9.6 ± 1.1 versus 7.1 ± 1.0); Oxford grading (0.5 ± 0.1 versus 3.6 ± 0.8); ferning test (2 ± 1 versus 2.4 ± 0.5); and Schirmer test I (14.6 ± 1.1 versus 12 ± 2.1), with P < 0.05 for all variables (Friedman and Wilcoxon tests). Tolerability was high, with no adverse events noted. Conclusions: A two-month treatment with Xiloial showed good tolerance and appeared to reduce ocular surface damage and symptoms of discomfort.

Frequency doubling technology, optical coherence technology and pattern electroretinogram in ocular hypertension

BackgroundTo assess which of three methods, namely, optical coherence tomography (OCT), pattern electroretinogram (PERG) or frequency-doubling technology (FDT), is the most sensitive and specific for detecting early glaucomatous damage in ocular hypertension (OH).MethodsFifty-two patients with OH (24 men and 28 women, mean age of 56 ± 9.6 years) with an intraocular pressure (IOP) > 21 mmHg and fifty-two control patients (25 men and 27 women, mean age of 54.8 ± 10.4 years) with IOP < 21 mmHg, were assessed. All the patients had normal visual acuity, normal optic disk and normal perimetric indices.All subjects underwent OCT, FDT and PERG. Data were analyzed with unpaired t-tests, Chi-square test and Receiver Operating Characteristic (ROC) curve analyses.ResultsIn patients with OH, OCT showed retinal nerve fiber layer (RNFL) thinner than in control group in the superior quadrant (130.16 ± 10.02 vs 135.18 ± 9.27 μm, respectively; p < 0.011) and inferior quadrant (120.14 ± 11.0 vs 132.68 ± 8.03 μm; p < 0.001). FDT showed a significantly higher pattern standard deviation (PSD) (3.46 ± 1.48 vs 1.89 ± 0.7 dB; p < 0.001). With respect to PERG, only the amplitude showed significant differences (p < 0.044) between the two groups. ROC curve analysis revealed a sensitivity and specificity of 92% and 86%, respectively, for FDT-PSD (with an area under the ROC curve of 0.940), whereas with OCT, a sensitivity of 82% and a specificity of 74% was recorded in the inferior RNFL quadrant (with an area under the ROC curve of 0.806) finally with PERG amplitude we found a sensitivity of 52% and specificity of 77% (with an area under the ROC curve of 0.595).ConclusionsFDT is the most sensitive and specific method for detecting early glaucomatous damage in eyes with OH, and together with OCT, can be useful in identifying those patients who may develop glaucoma.Trial registrationISRCT number: ISRCTN70295497

Hemorrhagic Occlusive Retinal Vasculitis After First Eye Cataract Surgery Without Subsequent Second Eye Involvement.

A case of monocular postoperative hemorrhagic occlusive retinal vasculitis (HORV) after uncomplicated bilateral cataract surgery is described. HORV is a severe syndrome that leads to painless visual loss after uncomplicated cataract surgery. The same surgical procedure was adopted in both eyes except for the use of intracameral vancomycin, which was injected only in the eye that developed HORV. Diffuse retinal ischemia with vascular sheathing and intraretinal hemorrhages were detected during the fourth postoperative day. Despite treatment, the patient developed severe neovascular glaucoma. This case supports the causative role of vancomycin in the pathogenesis of HORV and suggests avoiding it for chemoprophylaxis. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:764-766.].

Changes in Choroidal Thickness follow the RNFL Changes in Leber’s Hereditary Optic Neuropathy

Leber’s hereditary optic neuropathy (LHON) is typically characterized by vascular alterations in the acute phase. The aim of this study was to evaluate choroidal changes occurring in asymptomatic, acute and chronic stages of LHON. We enrolled 49 patients with LHON, 19 with Dominant Optic Atrophy (DOA) and 22 healthy controls. Spectral Domain-Optical Coherence Tomography (SD-OCT) scans of macular and peripapillary regions were performed in all subjects, to evaluate macular and peripapillary choroidal thickness, and retinal nerve fiber layer (RNFL) thicknes. Macular and peripapillary choroidal thicknesses were significantly increased in the acute LHON stage. On the contrary, macular choroidal thickness was significantly reduced in the chronic stage. Furthermore, peripapillary choroidal thickness was decreased in chronic LHON and in DOA. Both RNFL and choroid had the same trend (increased thickness, followed by thinning), but RNFL changes preceded those affecting the choroid. In conclusion, our study quantitatively demonstrated the involvement of the choroid in LHON pathology. The increase in choroidal thickness is a feature of the LHON acute stage, which follows the thickening of RNFL. Conversely, thinning of the choroid is the common outcome in chronic LHON and in DOA.