Acute macular neuroretinopathy following Valsalva manoeuvre: an insight into the pathophysiology.

Acute macular neuroretinopathy (AMN) affects the outer retina and is most likely induced by non-inflammatory ischaemia of the retinal deep capillary plexus and choriocapillaris. A man in his early 20s developed Valsalva retinopathy following weightlifting at the gym and presented with blurring of vision in the left eye 1 month after the initial retinal haemorrhages had resolved. A diffuse, purplish, donut-shaped, perifoveal lesion was seen on funduscopy and was well defined by an optical coherence tomography angiography (OCTA) en face image in the left eye. Outer retinal changes on optical coherence tomography (OCT) and a dense co-localised scotoma on a visual field (VF) examination confirmed the diagnosis of AMN, and the patient was started on a tapering dose of oral steroids. Improvement was seen in OCT, OCTA and VF during the 6-month follow-up visit. The use of OCTA en face imaging enabled the accurate identification of the lesion in the affected layers of the retina.

Predictors of late lumen enlargement after drug-coated balloon angioplasty for de novo coronary lesions.

BACKGROUND: Late lumen enlargement (LLE) - a positive remodelling phenomenon - after drug-coated balloon (DCB) angioplasty for stable coronary disease contributes to a lower restenosis rate. However, lesion characteristics promoting LLE remain unclear. AIMS: This study aimed to investigate predictive lesion characteristics for LLE using serial optical frequency domain imaging (OFDI) following DCB angioplasty for de novo coronary artery lesions. METHODS: This retrospective, single-centre observational study included patients with angina pectoris who underwent paclitaxel-coated balloon angioplasty without stenting under OFDI guidance as well as follow-up OFDI. OFDI endpoints were lumen volume, plaque phenotype, and procedure-associated dissection. LLE was defined as a ≥10% increase in the lumen volume of the treated lesion at follow-up. RESULTS: Between August 2016 and December 2019, among patients with successful DCB angioplasty, 108 lesions (83 patients) had available follow-up imaging after a median of 6.1 months. LLE was detected in 44 (40.7%) lesions. Fibrous/fibrocalcific and layered plaques had significantly larger lumen volumes at follow-up than immediately after the index procedure, whereas lipid plaques exhibited no significant difference. Medial dissection with an arc >90° revealed an increased lumen volume. Multivariate analysis showed that layered plaques (odds ratio [OR] 8.73, 95% confidence interval [CI]: 1.92-39.7; p=0.005) and medial dissection with an arc >90° (OR 4.65, 95% CI: 1.63-13.3; p=0.004) were independent LLE predictors. CONCLUSIONS: Layered plaques and extensive medial dissection after DCB angioplasty were associated with higher LLE occurrence in de novo coronary lesions. These findings may be clinically applicable to DCB therapeutic strategies based on plaque features.

Quantification of attenuation and speckle features from endoscopic OCT images for the diagnosis of human brain glioma.

Application of optical coherence tomography (OCT) in neurosurgery mostly includes the discrimination between intact and malignant tissues aimed at the detection of brain tumor margins. For particular tissue types, the existing approaches demonstrate low performance, which stimulates the further research for their improvement. The analysis of speckle patterns of brain OCT images is proposed to be taken into account for the discrimination between human brain glioma tissue and intact cortex and white matter. The speckle properties provide additional information of tissue structure, which could help to increase the efficiency of tissue differentiation. The wavelet analysis of OCT speckle patterns was applied to extract the power of local brightness fluctuations in speckle and its standard deviation. The speckle properties are analysed together with attenuation ones using a set of ex vivo brain tissue samples, including glioma of different grades. Various combinations of these features are considered to perform linear discriminant analysis for tissue differentiation. The results reveal that it is reasonable to include the local brightness fluctuations at first two wavelet decomposition levels in the analysis of OCT brain images aimed at neurosurgical diagnosis.

Follow-up report of fundus findings of tuberous sclerosis-associated retinal astrocytoma of two siblings.

A late adolescent with tuberous sclerosis (TS) presented with reduced vision in one eye to our tertiary care university hospital 4 years ago. Fundus examination revealed multiple retinal astrocytic hamartomas (RAHs) in both eyes. His younger sibling, who also had TS, was found to have RAH on retinal screening. The swept-source optical coherence tomography (SS-OCT) findings were typical of RAH. We further noted that some of the RAH lesions showed segmental whitening of the outer walls of the arterioles, which traversed through them. The segmental whitening may suggest the enveloping of normal retinal vessels by the tumour. En-face and B-scan SS-OCT angiography of patients with TS showed vascularity within the tumour. The vessels within the tumour appeared to be in continuity with the retinal vasculature. Both siblings were reviewed annually. At the end of 4 years, there was no change in visual acuity, tumour size, number, vascularity and behaviour.

Corneal Stroma Analysis and Related Ocular Manifestations in Recovered COVID-19 Patients.

Purpose: The purpose of this study was to assess the impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on corneal stroma characteristics, ocular manifestations, and post-recovery refractive surgery outcomes after varying recovery durations. Methods: Fresh corneal lenticules from patients with post-coronavirus disease 2019 (COVID-19; recovered within 135 days) and healthy controls (HCs) after small incision lenticule extraction (SMILE) surgery were obtained for experimental validation of SARS-CoV-2 susceptibility, morphological changes, and immune response of the corneal stroma. Corneal optical density (CD) was measured using the Pentacam HR. Corneal epithelium thickness (ET) and endothelium parameters were evaluated by wide-field optical coherence tomography (OCT) and non-contact specular microscopy (SP-1P), respectively. All the patients were assessed after SMILE surgery until 3 month of follow-up. Results: The cornea was susceptible to SARS-CoV-2 with the presence of SARS-CoV-2 receptors (CD147 and ACE2) and spike protein remnants (4 out of 58) in post-recovery corneal lenticules. Moreover, SARS-CoV-2 infection triggered immune responses in the corneal stroma, with elevated IL-6 levels observed between 45 and 75 days post-recovery, which were then lower at around day 105. Concurrently, corneal mid-stromal nerve length and branching were initially higher in the 60D to 75D group and returned to control levels by day 135. A similar trend was observed in CD within zones 0 to 2 and 2 to 6 and in the hexagonal cells (HEX) ratio in endothelial cells, whereas ET remained consistent. Notably, these changes did not affect the efficacy, safety, or predictability of post-recovery SMILE surgery. Conclusions: SARS-CoV-2 induces temporal alterations in corneal stromal morphology and function post-recovery. These findings provided a theoretical basis for corneal health and refractive surgery management in the post-COVID-19 milieu.

[Multimodal topographically oriented approach to the study of full-thickness macular holes]. / Mul'timodal'nyi topograficheski orientirovannyi podkhod k izucheniyu skvoznykh makulyarnykh razryvov.

PURPOSE: This article studies the relationship between structural changes according to the findings of optical coherence tomography (OCT) and OCT angiography (OCTA), microperimetry (MP), multifocal electroretinography (mfERG) parameters in topographically corresponding areas of the macular region in idiopathic full-thickness macular holes (FTMH). MATERIAL AND METHODS: OCT, OCTA, MP and mfERG were performed in 14 eyes with FTMH stages I-IV according to Gass. In 13 points at a distance of 0-2.5°, 2.5-5.0°, and 5.0-10.0° from the fixation point, the light sensitivity (LS), amplitude and latency of the P1 component were compared with the size of the hole, the area of cystic changes (CC) at the level of the inner nuclear layer (INL) and the outer plexiform layer and Henle fiber layer complex (OPL+HFL), vessel density in the superficial and deep capillary plexus (SCP and DCP). RESULTS: LS and P1 component amplitude were significantly reduced at a distance of up to 5.0° from the fixation point. LS correlates with the apical and basal diameter of the hole (R> -0.53), the area of CC in the INL (R> -0.62) and the OPL+HFL complex (R> -0.55), the density of vessels in the SCP at a distance of up to 2.5° from the fixation point (R>0.51) and in the DCP at a distance of up to 5° from the fixation point (R>0.49). The P1 amplitude correlates with the basal diameter of the hole (R= -0.38), the area of CC in the INL and the OPL+HFL complex (R> -0.33) and vessel density in the SCP (R=0.37) at a distance of up to 2.5° from the fixation point, as well as vessel density in the DCP at a distance of up to 5° from the fixation point (R=0.47). Vessel density in the DCP is significantly lower in the presence of CC in the retina (p<0.001). CONCLUSION: In FTMH, there is a relationship between bioelectrical activity and LS, and structural disorders, capillary perfusion in different layers of the retina. A multimodal topographically oriented approach allows studying the relationship between structural and functional parameters in individual points of the retina and can be used in monitoring of FTMH after surgical treatment.

[Optical coherence tomography angiography in the diagnosis of multiple sclerosis]. / Opticheskaya kogerentnaya tomografiya-angiografiya v diagnostike rasseyannogo skleroza.

PURPOSE: This study analyzes the main changes in retinal microcirculation in patients with multiple sclerosis (MS) and their relationship with the type of disease course. MATERIAL AND METHODS: 159 patients (318 eyes) were examined. The groups were formed according to the type of course and duration of MS: group 1 - 37 patients (74 eyes; 23.27%) with relapsing-remitting MS (RRMS) less than 1 year; group 2 - 47 patients (94 eyes; 29.56%) with RRMS from 1 year to 10 years; group 3 - 44 patients (86 eyes; 27.05%) with RRMS >10 years; group 4 - 32 patients (64 eyes; 20.12%) with secondary progressive MS (SPMS). Subgroups A and B were allocated within each group depending on the absence or presence of optic neuritis (ON). Patients underwent standard ophthalmological examination, including optical coherence tomography angiography (OCTA). RESULTS: A decrease in the vessel density (wiVD) and perfusion density (wiPD) in the macular and peripapillary regions was revealed, progressing with the duration of the disease and with its transition to the progressive type. The minimum values were observed in patients with SPMS (group 4), with the most pronounced in the subgroup with ON (wiVD = 16.06±3.65 mm/mm2, wiPD = 39.38±9.46%, ppwiPD = 44.06±3.09%, ppwiF = 0.41±0.05). CONCLUSION: OCTA provides the ability to detect subclinical vascular changes and can be considered a comprehensive, reliable method for early diagnosis and monitoring of MS progression.

Chemically induced cone degeneration in the 13-lined ground squirrel.

Animal models of retinal degeneration are critical for understanding disease and testing potential therapies. Inducing degeneration commonly involves the administration of chemicals that kill photoreceptors by disrupting metabolic pathways, signaling pathways, or protein synthesis. While chemically induced degeneration has been demonstrated in a variety of animals (mice, rats, rabbits, felines, 13-lined ground squirrels (13-LGS), pigs, chicks), few studies have used noninvasive high-resolution retinal imaging to monitor the in vivo cellular effects. Here, we used longitudinal scanning light ophthalmoscopy (SLO), optical coherence tomography, and adaptive optics SLO imaging in the euthermic, cone-dominant 13-LGS (46 animals, 52 eyes) to examine retinal structure following intravitreal injections of chemicals, which were previously shown to induce photoreceptor degeneration, throughout the active season of 2019 and 2020. We found that iodoacetic acid induced severe pan-retinal damage in all but one eye, which received the lowest concentration. While sodium nitroprusside successfully induced degeneration of the outer retinal layers, the results were variable, and damage was also observed in 50% of contralateral control eyes. Adenosine triphosphate and tunicamycin induced outer retinal specific damage with varying results, while eyes injected with thapsigargin did not show signs of degeneration. Given the variability of damage we observed, follow-up studies examining the possible physiological origins of this variability are critical. These additional studies should further advance the utility of chemically induced photoreceptor degeneration models in the cone-dominant 13-LGS.

A case of choroidal neovascularization as a first manifestaion of systemic lupus erythematosus.

BACKGROUND: To report a rare occurrence of pigment epitheliopathy associated with choroidal neovasculization as a first manifestation of systemic lupus erythematosus. CASE PRESENTATION: A 54-year-old female, with no prior medical history, sought a second opinion due to sudden drop in vision in her right eye to 20/80. Slit lamp examination was normal. Fundus examination revealed the presence of a subretinal hemorrhage in the macular area. Fundus imaging including optical coherence tomography and fluorescein angiography showed multifocal retinal pigment epitheliopathy associated with choroidal neovascularization (CNV). The patient had received an intravitreal injection of Bevacizumab 2 weeks ago. It was decided to complete the loading dose regimen with two additional Bevacizumab injections, and the first injection was done 2 weeks after her presentation. Two weeks later, the patient reported a rash on her cheeks, painful joints, and purpura. Systemic workup revealed positive ANA, anti-cardiolipin antibodies, and decreased complement levels, with negative anti-histone antibodies. This led to the diagnosis of systemic lupus erythematosus (SLE) based on the "Systemic Lupus International Collaborating Clinics" criteria. The patient was treated with 50 mg of prednisolone which was then tapered. 1 month after the third injection, an showed a total resolution of the sub-retinal fluid with an improvement of vision to 20/20. No recurrence was observed during follow-up. CONCLUSION: Based on the findings from the fundus exam and imaging, systemic symptoms and the blood work-up, we postulate that the pigment epitheliopathy associated with choroidal neovascularization was related to the vaso-occlusive disease at the level of the choroid that can be part of SLE vasculopathy. To our knowledge, this represents the first case in which pigment epitheliopathy and CNV were the primary manifestations of SLE.

The prone position in COVID-19 impacts the thickness of peripapillary retinal nerve fiber layers and macular ganglion cell layers.

The prone position reduces mortality in severe cases of COVID-19 with acute respiratory distress syndrome. However, visual loss and changes to the peripapillary retinal nerve fiber layer (p-RNFL) and the macular ganglion cell layer and inner plexiform layer (m-GCIPL) have occurred in patients undergoing surgery in the prone position. Moreover, COVID-19-related eye problems have been reported. This study compared the p-RNFL and m-GCIPL thicknesses of COVID-19 patients who were placed in the prone position with patients who were not. This prospective longitudinal and case-control study investigated 15 COVID-19 patients placed in the prone position (the "Prone Group"), 23 COVID-19 patients not in the prone position (the "Non-Prone Group"), and 23 healthy, non-COVID individuals without ocular disease or systemic conditions (the "Control Group"). The p-RNFL and m-GCIPL thicknesses of the COVID-19 patients were measured at 1, 3, and 6 months and compared within and between groups. The result showed that the Prone and Non-Prone Groups had no significant differences in their p-RNFL thicknesses at the 3 follow-ups. However, the m-GCIPL analysis revealed significant differences in the inferior sector of the Non-Prone Group between months 1 and 3 (mean difference, 0.74 µm; P = 0.009). The p-RNFL analysis showed a significantly greater thickness at 6 months for the superior sector of the Non-Prone Group (131.61 ± 12.08 µm) than for the Prone Group (118.87 ± 18.21 µm; P = 0.039). The m-GCIPL analysis revealed that the inferior sector was significantly thinner in the Non-Prone Group than in the Control Group (at 1 month 80.57 ± 4.60 versus 83.87 ± 5.43 µm; P = 0.031 and at 6 months 80.48 ± 3.96 versus 83.87 ± 5.43 µm; P = 0.044). In conclusion, the prone position in COVID-19 patients can lead to early loss of p-RNFL thickness due to rising intraocular pressure, which is independent of the timing of prone positioning. Consequently, there is no increase in COVID-19 patients' morbidity burden.

Intraoperative quantitative crystalline lens nuclear opacities analysis based on crystalline lenSx platform.

PURPOSE: The main objective is to quantify the lens nuclear opacity using spectral-domain optical coherence tomography (SD-OCT) and to evaluate its association with Lens Opacities Classification System III (LOCS-III) system, lens thickness (LT), and surgical parameters. The secondary objective is to assess the diagnostic model performance for hard nuclear cataract. METHODS: This study included 70 eyes of 57 adults with cataract, with 49 (70%) and 21 (30%) in training and validation cohort, respectively. Correlations of the average nuclear density (AND) /maximum nuclear density (MND) with LOCS-III scores, LT, and surgical parameters were analyzed. Univariate and multivariate logistic regression analysis, receiver operating characteristic curves and calibration curves were performed for the diagnostic of hard nuclear cataract. RESULTS: The pre-operative uncorrected distance visual acuity (UDVA), intraocular pressure (IOP), mean axial length (AL), and LT were 1.20 ± 0.47 log MAR, 15.50 ± 2.87 mmHg, 27.34 ± 3.77 mm and 4.32 ± 0.45 mm, respectively. The average nuclear opalescence (NO) and nuclear colour (NC) scores were 3.61 ± 0.94 and 3.50 ± 0.91 (ranging from 1.00 to 6.90), respectively. The average AND and MND were 137.94 ± 17.01 and 230.01 ± 8.91, respectively. NC and NO scores both significantly correlated with the AND (rNC = 0.733, p = 0.000; rNO = 0.755, p = 0.000) and MND (rNC = 0.643, p = 0.000; rNO = 0.634, p = 0.000). In the training cohort, the area under the curve (AUC) of the model was 0.769 (P < 0.001, 95%CI 0.620-0.919), which had a good degree of differentiation (Fig. 2a). The calibration curve showed good agreement between predicted and actual probability. CONCLUSION: The nuclear density measurement on SD-OCT images can serve as an objective and reliable indicator for quantifying nuclear density.

Generalized 3D registration algorithm for enhancing retinal optical coherence tomography images.

Significance: Optical coherence tomography (OCT) has emerged as the standard of care for diagnosing and monitoring the treatment of various ocular disorders due to its noninvasive nature and in vivo volumetric acquisition capability. Despite its widespread applications in ophthalmology, motion artifacts remain a challenge in OCT imaging, adversely impacting image quality. While several multivolume registration algorithms have been developed to address this issue, they are often designed to cater to one specific OCT system or acquisition protocol. Aim: We aim to generate an OCT volume free of motion artifacts using a system-agnostic registration algorithm that is independent of system specifications or protocol. Approach: We developed a B-scan registration algorithm that removes motion and corrects for both translational eye movements and rotational angle differences between volumes. Tests were carried out on various datasets obtained from two different types of custom-built OCT systems and one commercially available system to determine the reliability of the proposed algorithm. Additionally, different system specifications were used, with variations in axial resolution, lateral resolution, signal-to-noise ratio, and real-time motion tracking. The accuracy of this method has further been evaluated through mean squared error (MSE) and multiscale structural similarity index measure (MS-SSIM). Results: The results demonstrate improvements in the overall contrast of the images, facilitating detailed visualization of retinal vasculatures in both superficial and deep vasculature plexus. Finer features of the inner and outer retina, such as photoreceptors and other pathology-specific features, are discernible after multivolume registration and averaging. Quantitative analyses affirm that increasing the number of averaged registered volumes will decrease MSE and increase MS-SSIM as compared to the reference volume. Conclusions: The multivolume registered data obtained from this algorithm offers significantly improved visualization of the retinal microvascular network as well as retinal morphological features. Furthermore, we have validated that the versatility of our methodology extends beyond specific OCT modalities, thereby enhancing the clinical utility of OCT for the diagnosis and monitoring of ocular pathologies.

Cutting-edge issues in sympathetic ophthalmia approach and six case reports: a T cell-mediated autoimmune response.

Sympathetic ophthalmia is a rare and potentially devastating bilateral diffuse granulomatous panuveitis. It is caused by surgical or non-surgical eye injuries and is an uncommon and serious complication of trauma. It is diagnosed clinically and supported by imaging examinations such as ocular ultrasonography and optical coherence tomography. Its treatment consists of immunosuppressive therapy with steroids and sometimes steroid-sparing drugs, such as cyclosporine, azathioprine, cyclophosphamide, and mycophenolate mofetil. Fast and effective management with systemic immunosuppressive agents allows for disease control and achievement of good visual acuity in the sympathizing eye. By contrast, enucleation should be considered only in situations where the injured eye has no light perception or in the presence of severe trauma. In addition to a bibliographic review of this topic, we report six cases involving different immunosuppressive and surgical treatment modalities.

Optical coherence elastography under homolateral parallel acoustic radiation force excitation for ocular elasticity quantification.

Alteration in the elastic properties of biological tissues may indicate changes in the structure and components. Acoustic radiation force optical coherence elastography (ARF-OCE) can assess the elastic properties of the ocular tissues non-invasively. However, coupling the ultrasound beam and the optical beam remains challenging. In this Letter, we proposed an OCE method incorporating homolateral parallel ARF excitation for measuring the elasticity of the ocular tissues. An acoustic-optic coupling unit was established to reflect the ultrasound beam while transmitting the light beam. The ARF excited the ocular tissue in the direction parallel to the light beam from the same side of the light beam. We demonstrated the method on the agar phantoms, the porcine cornea, and the porcine retina. The results show that the ARF-OCE method can measure the elasticity of the cornea and the retina, resulting in higher detection sensitivity and a more extensive scanning range.

Retinal Nerve Fiber Layer Damage Assessment in Glaucomatous Eyes Using Retinal Retardance Measured by Polarization-Sensitive Optical Coherence Tomography.

Purpose: To assess the diagnostic performance and structure-function association of retinal retardance (RR), a customized metric measured by a prototype polarization-sensitive optical coherence tomography (PS-OCT), across various stages of glaucoma. Methods: This cross-sectional pilot study analyzed 170 eyes from 49 healthy individuals and 68 patients with glaucoma. The patients underwent PS-OCT imaging and conventional spectral-domain optical coherence tomography (SD-OCT), as well as visual field (VF) tests. Parameters including RR and retinal nerve fiber layer thickness (RNFLT) were extracted from identical circumpapillary regions of the fundus. Glaucomatous eyes were categorized into early, moderate, or severe stages based on VF mean deviation (MD). The diagnostic performance of RR and RNFLT in discriminating glaucoma from controls was assessed using receiver operating characteristic (ROC) curves. Correlations among VF-MD, RR, and RNFLT were evaluated and compared within different groups of disease severity. Results: The diagnostic performance of both RR and RNFLT was comparable for glaucoma detection (RR AUC = 0.98, RNFLT AUC = 0.97; P = 0.553). RR showed better structure-function association with VF-MD than RNFLT (RR VF-MD = 0.68, RNFLT VF-MD = 0.58; z = 1.99; P = 0.047) in glaucoma cases, especially in severe glaucoma, where the correlation between VF-MD and RR (r = 0.73) was significantly stronger than with RNFLT (r = 0.43, z = 1.96, P = 0.050). In eyes with early and moderate glaucoma, the structure-function association was similar when using RNFLT and RR. Conclusions: RR and RNFLT have similar performance in glaucoma diagnosis. However, in patients with glaucoma especially severe glaucoma, RR showed a stronger correlation with VF test results. Further research is needed to validate RR as an indicator for severe glaucoma evaluation and to explore the benefits of using PS-OCT in clinical practice. Translational Relevance: We demonstrated that PS-OCT has the potential to evaluate the status of RNFL structural damage in eyes with severe glaucoma, which is currently challenging in clinics.

Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum and Novel Clinical Observations in 241 Patients.

Purpose: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene. Methods: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations. Results: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, or vitelliform macular dystrophy (11%), central areolar choroidal dystrophy (28%), pseudo-Stargardt pattern dystrophy (41%), and retinitis pigmentosa (25%). Symptom onset was earlier in retinitis pigmentosa as compared with pseudo-Stargardt pattern dystrophy (34 vs 44 years; P = 0.004). The median visual acuity was 0.18 logMAR (interquartile range, 0-0.54 logMAR) and 0.18 logMAR (interquartile range 0-0.42 logMAR) in the right and left eyes, respectively. ERG showed a significantly reduced amplitude across all components (P < 0.001) and a peak time delay in the light-adapted 30-Hz flicker and single-flash b-wave (P < 0.001). Twenty-two variants were novel. The central areolar choroidal dystrophy phenotype was associated with 13 missense variants. The remaining variants showed marked phenotypic variability. Conclusions: We described six distinct FAF phenotypes associated with variants in the PRPH2 gene. One FAF phenotype may have multiple ERG phenotypes, demonstrating a discordance between structure and function. Given the vast spectrum of PRPH2 disease our findings are useful for future clinical trials.