Journal of Ophthalmic & Vision Research最新文献

Purpose: This research intended to fabricate the thiolated chitosan-dextran nanoparticles (NPs) containing topotecan (TPH-CMD-TCS-NPs) to assess the ability of NPs in improving the efficacy of intravitreal chemotherapy of retinoblastoma in a rabbit xenograft model.

Methods: The coacervation process was used to produce the NPs. The cellular uptake of Cyanine-3 (CY3)-labeled NPs were investigated in human retinoblastoma Y79 cells using confocal microscopy. Also, the prepared TPH-CMD-TCS-NPs were tested in vitro by the tetrazolium dyes II (XTT) and flow cytometry in order to assess their cytotoxicity. In addition, a rabbit xenograft model of retinoblastoma was developed to test the antitumor effectiveness of TPH-CMD-TCS-NPs through intravitreal administration.

Results: NPs had a mean diameter, polydispersity index, and zeta potential of 30 $\pm$ 4 nm, 0.24 $\pm$ 0.03 and +10 $\pm$ 3 mV, respectively. NPs (IC50s 40.40 compared to 126.20 nM, P = 0.022) were more effective than free topotecan as a dose-based feature. The tumor reaction to intravitreal chemotherapy with NPs was measured by evaluating the percentage of necrosis in the tumor tissue (91 $\pm$ 2%) and vitreous seeds (89 $\pm$ 9%) through hematoxylin and eosin (H&E) staining. In comparison with the control group, the TPH-CMD-TCs-NPs treated group showed a significant decrease in tumor volume seven days after the intravitreal injection (P = 0.039). No significant changes were found in the ERG parameters after the intravitreal injection of TPH-CMD-TCs-NPs or TPH (P $>$ 0.05).

Conclusion: This investigation revealed definitive antitumor efficacy of TPH-CMD-TCS-NPs by intravitreal administration in the rabbit xenograft retinoblastoma model.

Purpose: Adenosine signaling modulates ocular inflammatory processes, and its antagonism mitigates neovascularization in both newborns and preclinical models of ocular neovascularization including age-related macular degeneration (AMD). The adenosine receptor expression patterns have not been well characterized in the human retina and choroid.

Methods: Here we examined the expression of adenosine receptor subtypes within the retina and choroid of human donor eyes with and without AMD. Antibodies specifically targeting adenosine receptor subtypes A1, A2A, A2B, and A3 were used to assess their expression patterns. Quantitative real-time PCR analysis was used to confirm gene expression of these receptors within the normal human retina and choroid.

Results: We found that all four receptor subtypes were expressed in several layers of the retina, and within the retinal pigment epithelium and choroid. The expression of A1 receptors was more prominent in the inner and outer plexiform layers, where microglia normally reside, and supported by RNA expression in the retina. A2A and A2B showed similar expression patterns with prominent expression in the vasculature and retinal pigment epithelium. No dramatic differences in expression of these receptors were observed in eyes from patients with dry or wet AMD compared to control, with the exception A3 receptors. Eyes with dry AMD lost expression of A3 in the photoreceptor outer segments compared with eyes from control or wet AMD.

Conclusion: The ocular presence of adenosine receptors is consistent with their proposed role in modulation of inflammation in both the retina and choroid, and their potential targeting for AMD treatment.

Purpose: To determine associated factors for keratoconus (KCN) in the Iranian population.

Methods: In this retrospective case-control study, 100 KCN patients and 200 age- and sex-matched individuals, who were either candidates for photorefractive keratectomy or healthy referrals from the Torfeh Eye Hospital, were included as the case and control groups, respectively. KCN patients were all registered at the Iranian National Registry of Keratoconus (KCNRegⓇ). Demographic characteristics, patients' symptoms and their habits, as well as systemic and ocular disorders were documented. Clinical examinations included best corrected visual acuity (BCVA) and refractive error measurements, biomicroscopic examination, and corneal imaging.

Results: In this case group, the frequency of mild, moderate, and severe KCN was 38%, 28%, and 34%, respectively. Parental consanguinity (odds ratio [OR] = 1.758, P = 0.029), positive familial history in patients' first degree (OR = 12.533, P $<$ 0.001) and second degree (OR = 7.52, P $<$ 0.001) relatives, vernal keratoconjunctivitis (OR = 7.510, P = 0.003), severe eye rubbing (OR = 10.625, P $<$ 0.001), and systemic diseases including migraine, hypertension, and thyroid disease (OR = 6.828, P = 0.021) were found as associated factors for KCN. Lesser frequency of KCN was observed in patients with Fars ethnicity (OR = 0.583, P = 0.042), with higher levels of wealth indices (OR = 0.31, P $<$ 0.001) and higher levels of education (OR = 0.18, P = 0.024).

Conclusion: Severe eye rubbing, vernal keratoconjunctivitis, parental consanguinity and positive familial history of KCN, low socioeconomic status, and low levels of education were significantly associated with KCN in our study population.

Purpose: To study the alterations on the lenticules extracted after femtosecond (Femto) small incision lenticule extraction (SMILE) versus the corneal free cap removed using a microkeratome.

Methods: The visuMax (500 kHz; laser energy: 180 nJ) was used for small-incision lenticule extraction. Free caps from human cadaveric corneas were excised by microkeratome. The collected lenticules were examined with the light and transmission electron microscope (TEM) for histological analysis, DNA fragmentation was assessed by agarose gel electrophoresis, DNA damage was evaluated using comet assay, and corneal proteins secondary structure was assessed by Fourier transform infrared spectroscopy (FTIR).

Results: Light microscopic examination showed the presence of more edematous stroma under Femto SMILE than under free cap with a percentage change of 101.6%. In the Femto SMILE group, TEM examination showed pyknotic keratocytes, disruption, and cavitation of the collagen arrays stromal area under Femto SMILE. The DNA fragmentation for the Femto SMILE group revealed one undefined band with a size of 1.1 Kbp. The comet assay analysis indicated the presence of 3% and 8.0% tailed cells for the free cap and Femto SMILE groups, respectively. The tail lengths were 1.33 $\pm$ 0.16 and 1.67 $\pm$ 0.13 µm (P $<$ 0.01), the percentage of tail DNA was 1.41 $\pm$ 0.18% (P $<$ 0.01) and 1.72 $\pm$ 0.15%, and the tail moments were 1.88 $\pm$ 0.12 AU and 2.87 $\pm$ 0.14 AU (P $<$ 0.001) for the free cap and Femto SMILE groups, respectively. FTIR spectroscopy of the Femto smile group revealed disorders in the secondary and tertiary structure of the proteins.

Conclusion: Femto SMILE technique induced more structural changes, DNA fragmentation, DNA damage, and corneal proteins secondary structure alteration than those induced by a microkeratome cutting. These changes may be attributed to the deep penetration of high energy levels to the corneal layer. These findings may highlight the potential impact of the Femto SMILE on the cornea and the necessity for managing the laser parameters used.

Purpose: In this study, an algorithm based on deep learning was presented to reduce the retinal nerve fiber layer (RNFL) segmentation errors in spectral domain optical coherence tomography (SD-OCT) scans using ophthalmologists' manual segmentation as a reference standard.

Methods: In this study, we developed an image segmentation network based on deep learning to automatically identify the RNFL thickness from B-scans obtained with SD-OCT. The scans were collected from Farabi Eye Hospital (500 B-scans were used for training, while 50 were used for testing). To remove the speckle noise from the images, preprocessing was applied before training, and postprocessing was performed to fill any discontinuities that might exist. Afterward, output masks were analyzed for their average thickness. Finally, the calculation of mean absolute error between predicted and ground truth RNFL thickness was performed.

Results: Based on the testing database, SD-OCT segmentation had an average dice similarity coefficient of 0.91, and thickness estimation had a mean absolute error of 2.23 $\pm$ 2.1 μm. As compared to conventional OCT software algorithms, deep learning predictions were better correlated with the best available estimate during the test period (r² = 0.99 vs r² = 0.88, respectively; P $<$ 0.001).

Conclusion: Our experimental results demonstrate effective and precise segmentation of the RNFL layer with the coefficient of 0.91 and reliable thickness prediction with MAE 2.23 $\pm$ 2.1 μm in SD-OCT B-scans. Performance is comparable with human annotation of the RNFL layer and other algorithms according to the correlation coefficient of 0.99 and 0.88, respectively, while artifacts and errors are evident.

Purpose: Currently, two major principles exist to create LASIK flaps: firstly, a strictly horizontal (2D) cut similar to the microkeratome-cut and secondly an angled cut with a "step-like" edge (3D). The strictly horizontal (2D) cut method can be performed using apparatus such as the low-energy FEMTO LDV Z8 laser and its predecessors which are specific to this type. Alternatively, the low-energy FEMTO LDV Z8 laser's 3D flap design creates an interlocking flap-interface surface which potentially contributes toward flap stability. In addition, the FEMTO LDV Z8 offers flap-position adjustments after docking (before flap-creation). The current study analyzed precision, safety, efficacy, as well as patient self-reported pain and comfort levels after applying two different types of LASIK flap morphologies which were created with a low-energy, high-frequency femtosecond (fs) laser device.

Methods: A prospective, interventional, randomized, contralateral eye, single-center comparison study was conducted from November 2019 to March 2020 at the Hamburg vision clinic/ zentrumsehstärke, Hamburg, Germany. Eleven patients and 22 eyes received low-energy fs LASIK treatment for myopia or myopic astigmatism in both eyes. Before the treatment, the eyes were randomized (one eye was treated with the 2D, the other eye with the 3D method).

Results: The mean central flap thickness one month after surgery was 110.7 $\pm$ 1.6 μm (2D) and 111.2 $\pm$ 1.7 μm (3D); P = 0.365 (2D vs 3D). Flap thickness measured at 13 different points resulted in no statistically significant differences between any of the measurement points within/between both groups; demonstrating good planarity of the flap was achieved using both methods. Despite not being statistically significant, the surgeons recognized an increase in the presence of an opaque bubble layer in the 3D flap eyes during surgery and some patients reported higher, yet not statistically significant, pain scores in the 3D flap eyes during the first hours after the treatment. Overall, safety- and efficacy indices were 1.03 and 1.03, respectively.

Conclusion: In this prospective, randomized, contralateral eye study, the low-energy fs laser yielded predictable lamellar flap thicknesses and geometry at one-month follow-up. Based on these results, efficacy and safety of the corresponding laser application, that is, 2D vs 3D, are equivalent.

Purpose: Presence of diabetes in glaucoma patients may influence findings while documenting the progression of glaucoma. We conducted the study to compare individual and combined effects of diabetes and glaucoma on macular thickness and ganglion cell complex thickness.

Methods: The present study is a cross-sectional analysis of 172 eyes of 114 individuals. The groups were categorized according to the following conditions: glaucoma, diabetes mellitus, both glaucoma and diabetes (`both' group), and none of these conditions (`none' group). Patients with diabetes did not have diabetic retinopathy (DR). We compared retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) thickness, foveal loss of volume (FLV), and global loss of volume (GLV) among the groups. We used random effects multivariate analysis to adjust for potential confounders.

Results: The mean (SD) age of these individuals was 60.7 (10.1) years. The total average RNFL and GCC were significantly lower in the glaucoma group (RNFL: -36.27, 95% confidence intervals [CI]: -42.79 to -29.74; P $<$ 0.05, and GCC: -26.24, 95% CI: -31.49 to -20.98; P $<$ 0.05) and the `both' group (RNFL: -24.74, 95% CI: -32.84 to -16.63; P $<$ 0.05, and GCC: -17.92, 95% CI: -24.58 to -11.26; P $<$ 0.05) as compared with the `none' group. There were no significant differences in the average RNFL values and total average GCC between the diabetes group and the `none' group. The values of FLV and GLV were significantly higher in the `glaucoma' group and the `both' group as compared with the `none' group. The foveal values were not significantly different across these four groups. Among the glaucoma cases, 25% were mild, 30% were moderate, and 45% were severe; there was no significant difference in the proportion of severity of glaucoma between the `glaucoma only' and `both' groups (p=0.32). After adjusting for severity and type of glaucoma, there were no statistically significant differences in the values of average RNFL (6.6, 95% CI: -1.9 to 15.2; P=0.13), total average GCC (3.6, -95% CI: -2.4 to 9.6; P=0.24), and GLV (-3.9, 95% CI: -9.5 to 1.6; P=0.16) in the `both group' as compared with the glaucoma only group.

Conclusion: We found that diabetes with no DR did not significantly affect the retinal parameters in patients with glaucoma. Thus, it is less likely that thickness of these parameters will be overestimated in patients with glaucoma who have concurrent diabetes without retinopathy.

Retinal pigment epithelium (RPE) is a monolayer of cells situated between photoreceptors and the underlying choroid. It is essential for normal retinal function. Damaged RPE is associated with diseases such as age-related macular degeneration, Stargardt's macular dystrophy, and retinitis pigmentosa. RPE cells can easily be visualized in vivo, sustainable in vitro, and differentiated from stem cells with a relatively straightforward protocol. Due to these properties and the clinical significance of this epithelium in various retinal diseases, RPE transplantation as a treatment modality has gained considerable interest in the last decade. This paper presents the main techniques for RPE transplantation and discusses recent clinically relevant publications.

Identification of ocular manifestations in patients with sensorineural hearing loss (SNHL) can have a large impact on the outcome and treatment of pediatric patients. Due to the common co-incidence of ocular manifestations and SNHL in children, both ophthalmologic and hearing loss screening and routine examinations must be conducted to minimize adverse outcomes and worsening of pathology. Early evaluation and diagnosis is imperative for intervention and further development of the patient. Co-incidence requires a thorough evaluation that includes a comprehensive history, examination, and diagnostic testing. In this article, a literature review was conducted to analyze the presentations of various diseases and syndromes, such as Alport Syndrome, Waardenburg Syndrome, Norrie Disease, Usher Disease, Stickler Syndrome, Marfan Syndrome, Congenital Rubella, and Hereditary Optic Neuropathies. We divided the various ocular pathologies into anterior and posterior segment presentations and associated systemic findings for better understanding. Additionally, this review aims to include an update on the management of patients with both ocular and hearing loss manifestations.

Purpose: To determine the relationship between road accidents with visual acuity, refractive errors, visual field, and contrast sensitivity.

Methods: This population-based case-control study was conducted on roads leading to Tehran Province, Iran. The case group comprised drivers who had met with accidents and were at fault for the accident. The cases were selected in an ongoing manner (incidence cases). The controls were drivers who were the opposing victims in the same. After an initial interview, optometric and ophthalmic examinations including the measurement of visual acuity, refraction, visual field assessment, contrast sensitivity measurement, and slit lamp biomicroscopy were performed for all study participants.

Results: In this study, 281 and 204 individuals were selected for the case and control groups. The mean uncorrected visual acuity was 0.05 $\pm$ 0.12 and 0.037 $\pm$ 0.10 logMAR in the case and control groups, respectively (P = 0.095). Of the participants in the case and control groups, 32.8% and 23% had a visual field defect in at least one eye, respectively (adjusted odds ratios [aOR] = 1.63, 95% confidence interval [CI]: 1.08-2.48; P = 0.021). Moreover, 16.2% of the cases and 8.3% of the controls had visual field defects in both eyes (aOR = 2.13, 95% CI: 1.17-3.86; P = 0.012). Contrast sensitivity was worse in the case group in all spatial frequencies under non-glare conditions. However, under glare conditions, the contrast sensitivity was significantly worse in the case group only in the spatial frequency of 12 cycles per degree (cpd).

Conclusion: Reduced contrast sensitivity, especially under non-glare conditions, and visual field defects are risk factors that influence the prevalence of road accidents. It is strongly advised that special attention be paid to these visual functions in legal assessments to apply the necessary interventions in individuals with these types of disorders.