-
Scientific Reports Aug 2023Macular edema (ME), the accumulation of intraretinal fluid in the macula, is a common sight affecting sequelae of retinitis pigmentosa (RP). However, it is unclear why...
Macular edema (ME), the accumulation of intraretinal fluid in the macula, is a common sight affecting sequelae of retinitis pigmentosa (RP). However, it is unclear why some patients develop ME, and others do not. This study aims to identify associations between clinical-genetic factors in RP with ME. Patients with clinically confirmed RP cases were identified from the inherited retinal disease database at a large tertiary referral academic center. Demographic and genetic testing findings were noted. Additionally, optical coherence tomography volume scans were graded using a validated grading system. One hundred and six patients (73.1%) were found to have ME in at least one eye (OD = 88, mean = 37.9%, OS = 98, mean = 31.7%). Structurally, the presence of epiretinal membrane (ERM) (p < 0.007) and vitreo-macular traction (VMT) (p < 0.003) were significantly associated with ME. Additionally, X-linked (p < 0.032) and autosomal dominant inheritance (p < 0.039) demonstrated a significant association with ME, with RP1 (p < 0.045) and EYS (p < 0.017) pathogenic variants also significantly associated with ME. This study, in a large cohort of RP patients, confirms previous retinal structural associations for ME in RP and identifies potential new genetic associations.
Topics: Humans; Macular Edema; Retinitis Pigmentosa; Retina; Retinal Diseases; Macula Lutea; Eye Proteins
PubMed: 37648803
DOI: 10.1038/s41598-023-41464-z -
International Journal of Molecular... Jan 2024Two-photon excitation microscopy (TPM) and multiphoton fluorescence microscopy (MPM) are advanced forms of intravital high-resolution functional microscopy techniques... (Review)
Review
Two-photon excitation microscopy (TPM) and multiphoton fluorescence microscopy (MPM) are advanced forms of intravital high-resolution functional microscopy techniques that allow for the imaging of dynamic molecular processes and resolve features of the biological tissues of interest. Due to the cornea's optical properties and the uniquely accessible position of the globe, it is possible to image cells and tissues longitudinally to investigate ocular surface physiology and disease. MPM can also be used for the in vitro investigation of biological processes and drug kinetics in ocular tissues. In corneal immunology, performed via the use of TPM, cells thought to be intraepithelial dendritic cells are found to resemble tissue-resident memory T cells, and reporter mice with labeled plasmacytoid dendritic cells are imaged to understand the protective antiviral defenses of the eye. In mice with limbal progenitor cells labeled by reporters, the kinetics and localization of corneal epithelial replenishment are evaluated to advance stem cell biology. In studies of the conjunctiva and sclera, the use of such imaging together with second harmonic generation allows for the delineation of matrix wound healing, especially following glaucoma surgery. In conclusion, these imaging models play a pivotal role in the progress of ocular surface science and translational research.
Topics: Animals; Mice; Cornea; Sclera; Microscopy, Fluorescence; Microscopy, Fluorescence, Multiphoton; Conjunctiva
PubMed: 38338948
DOI: 10.3390/ijms25031670 -
International Journal of Pharmaceutics Jun 2024Ocular delivery is the most challenging aspect in the field of pharmaceutical research. The major hurdle for the controlled delivery of drugs to the eye includes the... (Review)
Review
Ocular delivery is the most challenging aspect in the field of pharmaceutical research. The major hurdle for the controlled delivery of drugs to the eye includes the physiological static barriers such as the complex layers of the cornea, sclera and retina which restrict the drug from permeating into the anterior and posterior segments of the eye. Recent years have witnessed inventions in the field of conventional and nanocarrier drug delivery which have shown considerable enhancement in delivering small to large molecules across the eye. The dynamic challenges associated with conventional systems include limited drug contact time and inadequate ocular bioavailability resulting from solution drainage, tear turnover, and dilution or lacrimation. To this end, various bioactive-based nanosized carriers including liposomes, ethosomes, niosomes, dendrimer, nanogel, nanofibers, contact lenses, nanoprobes, selenium nanobells, nanosponge, polymeric micelles, silver nanoparticles, and gold nanoparticles among others have been developed to circumvent the limitations associated with the conventional dosage forms. These nanocarriers have been shown to achieve enhanced drug permeation or retention and prolong drug release in the ocular tissue due to their better tissue adherence. The surface charge and the size of nanocarriers (10-1000 nm) are the important key factors to overcome ocular barriers. Various nanocarriers have been shown to deliver active therapeutic molecules including timolol maleate, ampicillin, natamycin, voriconazole, cyclosporine A, dexamethasone, moxifloxacin, and fluconazole among others for the treatment of anterior and posterior eye diseases. Taken together, in a nutshell, this extensive review provides a comprehensive perspective on the numerous facets of ocular drug delivery with a special focus on bioactive nanocarrier-based approaches, including the difficulties and constraints involved in the fabrication of nanocarriers. This also provides the detailed invention, applications, biodistribution and safety-toxicity of nanocarriers-based therapeutcis for the ophthalmic delivery.
Topics: Animals; Humans; Administration, Ophthalmic; Biological Availability; Drug Carriers; Drug Delivery Systems; Drug Liberation; Eye; Eye Diseases; Nanoparticle Drug Delivery System; Nanoparticles
PubMed: 38703931
DOI: 10.1016/j.ijpharm.2024.124192 -
Translational Vision Science &... Oct 2023The purpose of this study was to explore two-dimensional peripheral refraction and higher-order aberrations (HOAs) induced by orthokeratology lens decentration.
PURPOSE
The purpose of this study was to explore two-dimensional peripheral refraction and higher-order aberrations (HOAs) induced by orthokeratology lens decentration.
METHODS
Two-dimensional peripheral refraction and HOAs in a rectangular field (horizontally 60 degrees and vertically 36 degrees) were obtained using an open-view Hartmann-Shack wavefront sensor. The peripheral field was divided into 8 regions according to a combination of superior (UZ) or inferior (LZ) and a value, 1 (T25 to T30), 2 (T20 to T25), 3 (N20 to N25), or 4 (N25 to N30). The decentration of the lens was evaluated based on the change of power in the front of the tangential corneal map. All measurements were taken at the baseline and 1 month after lens fitting.
RESULTS
In total, 134 myopic children (age = 12.47 ± 1.70 years, SER = -2.44 ± 1.10 diopters [D]) were recruited. In general, horizontally asymmetrical change was observed in relative peripheral refraction (RPR), spherical aberration (SA), and horizontal coma. The root-mean square of higher order aberration (RMSHOA) and vertical coma demonstrated radial symmetrical change and vertically asymmetric change, respectively. Relative peripheral myopia was significantly increased after the treatment, with more myopic refraction in the temporal side. RPR changes in UZ2, UZ3, UZ4, LZ1, and LZ2 were related to the amount of lens decentration (r ≈ 0.4, P < 0.05). All HOAs increased after lens fitting (around 0.03 um, 0.02 um, 0.04 um, and 0.41 um for SA, horizontal COMA, vertical COMA, and RMSHOA in the periphery region).
CONCLUSIONS
RPR and HOAs are related to lens decentration, which might contribute to the efficacy of orthokeratology.
TRANSLATIONAL RELEVANCE
The study found a decentration-related optical feature after 1 month of lens wear, which is a suggested protective factor in myopia treatment. The findings might provide new insights for customized contact lens myopia treatment based on optics.
Topics: Child; Humans; Adolescent; Corneal Topography; Refraction, Ocular; Vision Tests; Cornea; Myopia; Vision Disorders
PubMed: 37824110
DOI: 10.1167/tvst.12.10.8 -
Translational Vision Science &... Apr 2024Subdamaging thermal retinal laser therapy has the potential to induce regenerative stimuli in retinal diseases, but validated dosimetry is missing. Real-time...
PURPOSE
Subdamaging thermal retinal laser therapy has the potential to induce regenerative stimuli in retinal diseases, but validated dosimetry is missing. Real-time optoacoustic temperature determination and control could close this gap. This study investigates a first in vivo application.
METHODS
Two iterations of a control module that were optically coupled in between a continuous-wave commercial laser source and a commercial slit lamp were evaluated on chinchilla rabbits. The module allows extraction of the temperature rise in real time and can control the power of the therapy laser such that a predefined temperature rise at the retina is quickly achieved and held constant. Irradiations with aim temperatures from 45°C to 69°C were performed on a diameter of 200 µm and a heating time of 100 ms.
RESULTS
We analyzed 424 temperature-guided irradiations in nine eyes of five rabbits. The mean difference between the measured and aim temperature was -0.04°C ± 0.98°C. The following ED50 values for visibility thresholds could be determined: 58.6°C for funduscopic visibility, 57.7°C for fluorescein angiography, and 57.0°C for OCT. In all measurements, the correlation of tissue effect was higher to the temperature than to the average heating laser power used.
CONCLUSIONS
The system was able to reliably perform temperature-guided irradiations, which allowed for better tissue effect control than simple power control. This approach could enhance the accuracy, safety, and reproducibility of thermal stimulating laser therapy.
TRANSLATIONAL RELEVANCE
This study is a bridge between preclinical ex vivo experiments and a pilot clinical study.
Topics: Rabbits; Animals; Temperature; Reproducibility of Results; Retina; Retinal Diseases; Fluorescein Angiography
PubMed: 38639930
DOI: 10.1167/tvst.13.4.26 -
Eye (London, England) Feb 2024Describe vitreomacular interface abnormalities (VMIA) using spectral-domain optical coherence tomography (SD-OCT), and correlations with age-related macular degeneration...
BACKGROUND/OBJECTIVE
Describe vitreomacular interface abnormalities (VMIA) using spectral-domain optical coherence tomography (SD-OCT), and correlations with age-related macular degeneration (AMD) grade in Ghanaian Africans.
SUBJECTS/METHODS
Prospective, cross-sectional study of adults aged ≥50 years recruited in Ghana AMD Study. Participant demographics, medical histories, ophthalmic examination, digital colour fundus photography (CFP) were obtained. High-resolution five-line raster OCT, Macular Cube 512 × 128 scans, and additional line scans in areas of clinical abnormality, were acquired. SD-OCT VMI features classified by International Vitreomacular Traction Study Group system and relationships to AMD grade were evaluated.
OUTCOMES
VMIA prevalence, posterior vitreous detachment (PVD), vitreomacular adhesions (VMA), vitreomacular traction (VMT), epiretinal membranes (ERM), correlations with AMD grade.
RESULTS
The full Ghana AMD cohort included 718 participants; 624 participants (1248 eyes) aged ≥50 years (range = 50-101, mean = 68.8), 68.9% female were included in this analysis. CFP with OCT scans were available for 776 eyes (397 participants); 707 (91.1%) had gradable CFP and OCT scans for both AMD and VMI grading forming the dataset for this report. PVD was absent in 504 (71.3%); partial and complete PVD occurred in 16.7% and 12.0% respectively. PVD did not increase with age (p = 0.720). VMIA without traction and macular holes were observed in 12.2% of eyes; 87.8% had no abnormalities. VMIA was not significantly correlated with AMD grade (p = 0.819).
CONCLUSIONS
This provides the first assessment of VMIA in Ghanaian Africans. VMIA are common in Africans; PVD may be less common than in Caucasians. There was no significant association of AMD grade with VMIA.
Topics: Adult; Humans; Female; Male; Ghana; Vitreous Body; Macula Lutea; Prospective Studies; Cross-Sectional Studies; Vitreous Detachment; Eye Diseases; Macular Degeneration; Tomography, Optical Coherence; Retrospective Studies
PubMed: 37773435
DOI: 10.1038/s41433-023-02737-z -
Translational Vision Science &... Jun 2024To assess longitudinal reproducibility of metrics of foveal density (peak cone density [PCD], cone density centroid [CDC], and 80th percentile centroid area) in...
PURPOSE
To assess longitudinal reproducibility of metrics of foveal density (peak cone density [PCD], cone density centroid [CDC], and 80th percentile centroid area) in participants with normal vision.
METHODS
Participants (n = 19; five male and 14 female) were imaged at two time points (average interval of 3.2 years) using an adaptive optics scanning light ophthalmoscope (AOSLO). Foveally centered regions of interest (ROIs) were extracted from AOSLO montages. Cone coordinate matrices were semiautomatically derived for each ROI, and cone mosaic metrics were calculated.
RESULTS
On average, there were no significant changes in cone mosaic metrics between visits. The average ± SD PCD was 187,000 ± 20,000 cones/mm2 and 189,000 ± 21,700 cones/mm2 for visits 1 and 2, respectively (P = 0.52). The average ± SD density at the CDC was 183,000 ± 19,000 cones/mm2 and 184,000 ± 20,800 cones/mm2 for visits 1 and 2, respectively (P = 0.78). The average ± SD 80th percentile isodensity contour area was 15,400 ± 1800 µm2 and 15,600 ± 1910 µm2 for visits 1 and 2, respectively (P = 0.57).
CONCLUSIONS
Foveal cone mosaic density metrics were highly reproducible in the cohort examined here, although further study is required in more diverse populations.
TRANSLATIONAL RELEVANCE
Determination of the normative longitudinal changes in foveal cone topography is key for evaluating longitudinal measures of foveal cone topography in patients with progressive retinal dystrophies.
Topics: Humans; Retinal Cone Photoreceptor Cells; Male; Fovea Centralis; Female; Adult; Reproducibility of Results; Middle Aged; Cell Count; Young Adult; Ophthalmoscopy; Tomography, Optical Coherence; Visual Acuity
PubMed: 38913007
DOI: 10.1167/tvst.13.6.18 -
Ophthalmic & Physiological Optics : the... Nov 2023To compare axial length (AL) growth curves in East Asian (EA) and non-EA emmetropes. (Comparative Study)
Comparative Study Meta-Analysis
PURPOSE
To compare axial length (AL) growth curves in East Asian (EA) and non-EA emmetropes.
METHODS
A meta-regression of 28 studies with emmetrope-specific AL data (measured with optical biometry) was performed. Emmetropia was defined as spherical equivalent refraction (SER) between -0.50 and +1.25 D, determined under cycloplegia if the mean age was ≤20 years. The AL growth curve (mean AL vs. mean age) was first fitted to the full dataset using a weighted nonlinear mixed-effects model, before refitting the model with ethnicity as a two-level grouping variable (EA vs. non-EA). Ethnic differences in growth curve parameters were tested using the Wald test.
RESULTS
A total of 3331 EA and 1071 non-EA emmetropes (mean age: 6.5-23.1 years) were included. There was no evidence of an ethnic difference in either final AL (difference: 0.15 mm, 95% CI: -0.04 to 0.35 mm, p = 0.15) or initial AL, as represented by the amount that the final AL needed to be offset to obtain the y-intercept (difference: -2.77 mm, 95% CI: -10.97 to 5.44, p = 0.51). Likewise, AL growth rate (curve steepness) did not differ between ethnic groups (difference: 0.09, 95% CI: -0.13 to 0.31, p = 0.43). Collectively, AL growth rate decreased from 0.24 mm/year at 6 years of age to around 0.05 mm/year at 11 years of age, after which it dipped below the repeatability of optical biometry (±0.04 mm) and practically plateaued around 16 years of age (final AL: 23.60 mm).
CONCLUSIONS
EA and non-EA emmetropes have comparable AL growth curves.
Topics: Adolescent; Adult; Child; Humans; Young Adult; Axial Length, Eye; East Asian People; Emmetropia; Eye; Myopia; Refraction, Ocular
PubMed: 37368239
DOI: 10.1111/opo.13195 -
Comparative Medicine Oct 2023Large animal models are essential to research in facial paralysis, face transplant, craniofacial surgery, and ophthalmology. Pigs are a well-studied species with high...
Large animal models are essential to research in facial paralysis, face transplant, craniofacial surgery, and ophthalmology. Pigs are a well-studied species with high similarity to human anatomy and physiology for these research areas. However, in contrast to cats and dogs protecting the cornea and eye is difficult in swine due to the inability to use an Elizabethan collar (E-collar) and the complexity of placing and maintaining a temporary tarsorrhaphy for corneal protection due to the strength of the pig levator muscle. This study presents an effective method to provide corneal and eye protection in the domestic swine for at least 50 d. Furthermore, protection of the eye and face is achieved through the innovative use of a modified ophthalmologic face shield. The findings from this study will advance large animal research in these fields, enabling innovation in surgery and tissue engineering in areas of both craniofacial and ophthalmologic research.
Topics: Humans; Swine; Cats; Animals; Dogs; Cornea; Muscles; Models, Animal
PubMed: 38087405
DOI: 10.30802/AALAS-CM-22-000063 -
Genomics Jan 2024The death of retinal ganglion cells (RGCs) can cause irreversible injury in visual function. Clarifying the mechanism of RGC degeneration is critical for the development...
The death of retinal ganglion cells (RGCs) can cause irreversible injury in visual function. Clarifying the mechanism of RGC degeneration is critical for the development of therapeutic strategies. Circular RNAs (circRNAs) are important regulators in many biological and pathological processes. Herein, we performed circRNA microarrays to identify dysregulated circRNAs following optic nerve crush (ONC). The results showed that 221 circRNAs were differentially expressed between ONC retinas and normal retinas. Notably, the levels of circular RNA-Dcaf6 (cDcaf6) expression in aqueous humor of glaucoma patients were higher than that in cataract patients. cDcaf6 silencing could reduce oxidative stress-induced RGC apoptosis in vitro and alleviate retinal neurodegeneration in vivo as shown by increased neuronal nuclei antigen (NeuN, neuronal bodies) and beta-III-tubulin (TUBB3, neuronal filaments) staining and reduced glial fibrillary acidic protein (GFAP, activated glial cells) and vimentin (activated glial cells) staining. Collectively, this study identifies a promising target for treating retinal neurodegeneration.
Topics: Animals; Humans; Disease Models, Animal; Optic Nerve; Optic Nerve Injuries; Retina; Retinal Ganglion Cells; RNA, Circular
PubMed: 38163571
DOI: 10.1016/j.ygeno.2023.110776