Untreated Eyes Research Articles

Brightness perception changes related to pupil size

Dilating the pupils allow more quanta of light to impact the retina. Consequently, if one pupil is dilated with a pharmacological agent (Tropicamide), the brightness of a surface under observation should increase proportionally to the pupil dilation. Little is known about causal effects of changes in pupil size on perception of an object’s brightness. In a psychophysical procedure of brightness adjustment and matching, we presented to one eye geometrical patterns with a central square (the reference pattern) that differed in physical brightness within backgrounds of constant luminance. Subsequently, with the other eye, participants (n = 30) adjusted to the same luminance a similar pattern (target) whose central square luminance was randomly set higher or lower in brightness than the reference. As only one eye was treated with Tropicamide, we assessed whether the subjective brightness of the target square shifted in a consistent direction when viewed with the dilated pupil compared to the untreated (control) eye. We found that, as the pupil increased post drug administration, so significantly did the sense of brightness of the pattern (i.e., higher brightness adjustments followed viewing the reference pattern with the treated (Tropicamide) eye). A reversed effect was observed when the control eye viewed the reference pattern first. The results confirm that even slight pupil dilations can result in an enhanced perceptual experience of brightness of the attended object, corresponding to an average increase of 2.09 cd/m2 for each 1 mm increase in pupil diameter.

Intraocular Pressure Decrease Does Not Affect Blood Flow Rate of Ophthalmic Artery in Ocular Hypertension.

PurposeTo investigate if decrease of IOP affects the volumetric blood flow rate in the ophthalmic artery (OA) in patients with previously untreated ocular hypertension.MethodsSubjects with untreated ocular hypertension (n = 30; mean age 67 ± 8 years; 14 females) underwent ophthalmologic examination and a 3-Tesla magnetic resonance imaging investigation. The magnetic resonance imaging included three-dimensional high-resolution phase-contrast magnetic resonance imaging to measure the OA blood flow rate. The subjects received latanoprost once daily in the eye with higher pressure, the untreated eye served as control. The same measurements were repeated approximately 1 week later.ResultsThe mean OA blood flow rate before and after treatment was 12.4 ± 4.4 and 12.4 ± 4.6 mL/min in the treated eye (mean ± SD; P = 0.92) and 13.5 ± 5.2 and 13.4 ± 4.1 mL/min in the control eye (P = 0.92). There was no significant difference between the treated and control eye regarding blood flow rate before (P = 0.13) or after treatment (P = 0.18), or change in blood flow rate after treatment (0.1 ± 3.1 vs. −0.1 ± 4.0 mL/min, P = 0.84). Latanoprost decreased the IOP by 7.2 ± 3.1 mm Hg in the treated eye (P < 0.01).ConclusionsThe results indicate that a significant lowering of IOP does not affect the blood flow rate of the OA in ocular hypertension subjects. The ability to maintain blood supply to the eye independent of the IOP could be a protective mechanism in preserving vision in subjects with ocular hypertension.

Shifting hierarchy of the conjunctival florae in the patients employed a long-time topical fluoroquinolone.

To observe the shifting hierarchy of the conjunctival florae in the patients who employed a long-time topical fluoroquinolone and characterize the consequent variations of their antibiotic sensitivity and virulence. A total of 143 eyes (143 patients) who suffered from the non-infectious corneal ulcer and topically used fluoroquinolone more than 2wk were enrolled as the fluoroquinolone eye. The untreated fellow eye was considered as the contralateral eye. Seventy-five healthy subjects were selected as the control. The culture positivity and strains of the isolated conjunctival florae were observed. Their antibiotic susceptibility and expression of the virulence-related genes were detected. Florae were recovered from 84.0%, 37.1%, and 57.3% of the conjunctival swabs in the control, fluoroquinolone eye, and contralateral eye, respectively. The most frequently isolated microorganisms were Staphylococcus epidermidis (34.9%) in the control, followed by Staphylococcus aureus (17.5%), Staphylococcus saprophyticus (14.3%), Micrococcus (9.5%), Propionibacterium acnes (7.9%). However, those orderly ranks shifted to Staphylococcus aureus (34.0%), Propionibacterium acnes (20.8%), Candida albicans (17.0%), Pseudomonas aeruginosa (9.4%) in the fluoroquinolone eye. A growing number of the fluoroquinolone-resistant florae survived in the fluoroquinolone eye, accompanied by an increased expression of the virulence-related genes. A long-time topical fluoroquinolone leads to a shifting hierarchy of the conjunctival florae, accompanied by the consequent variations of the antibiotic sensitivity and virulence.

Influence of unilateral intravitreal bevacizumab injection on the incidence of symptomatic choroidal neovascularization in the fellow eye in patients with neovascular age-related macular degeneration (Review).

Neovascular age-related macular degeneration (neovascular ARMD) represents only 10% of ARMD cases but is responsible, if untreated, for quick and severe central vision loss due to major macular changes. The presence of choroidal neovascularization (CNV) in one eye is associated with an approximately 10% risk of CNV development in the fellow eye each year. Intravitreal anti-VEGF therapy has quickly evolved as the standard treatment in neovascular ARMD in the last decade due to significant anatomical and functional improvements, especially in the early stages. In many reports an improvement in the untreated fellow eye was mentioned and systemic exposure was soon confirmed for all anti-VEGF agents after unilateral intravitreal injection. In particular, bevacizumab intravitreal injection is followed by a consistent reduction of serum VEGF levels and the drug was shown to have the longest serum half-life raising important debates about its safety. Once bevacizumab was detected in the fellow eye of an animal model after unilateral injection, the possible influence on fellow eye conversion rate into neovascular ARMD was questioned. Although comparative studies have not found statistically significant differences between drugs regarding the incidence of symptomatic CNV in the fellow eye during treatment, we observed, on a retrospective 36-month evaluation, a reduced incidence of symptomatic CNV in the fellow eye that might be explained by the consistent systemic exposure of bevacizumab.

Efficacy of intravitreal AFlibercept injection For Improvement of retinal Nonperfusion In diabeTic retinopathY (AFFINITY study)

IntroductionTo evaluate the effects of intravitreal aflibercept injection on retinal nonperfusion in patients with diabetic retinopathy (DR) using ultrawide field (UWF) fluorescein angiography (FA).Research design and methodsThirty-eight eyes of 38...

Macular OCT Characteristics at 36 Weeks’ Postmenstrual Age in Infants Examined for Retinopathy of Prematurity

To report our ability to capture,-grade reliably, and analyze bedside macular OCT images from preterm infants and relate OCT findings to biological factors and retinopathy of prematurity (ROP) status at a single time window in the Study of Eye Imaging in Preterm Infants (BabySTEPS). Prospective, observational study. Preterm infants eligible for ROP screening with parental consent for research and a 36 ± 1 weeks' postmenstrual age (PMA) visit. We imaged both eyes of preterm infants with an investigational noncontact, handheld swept-source (SS) OCT at the time of clinical ROP examinations. Macular OCT features and layer thicknesses for untreated eyes of infants at 36 ± 1 weeks' PMA were compared with demographic data and clinical ROP examination performed by experts. Statistical analyses accounted for the use of both eyes of infants. Macular OCT features and layer thicknesses, gender, race or ethnicity, gestational age, birth weight, ROP stage, and plus disease. We captured macular OCT from 169 eyes (1 eye excluded because of prior ROP treatment) at36 ±1 weeks' PMA. The quality of OCT volumes was excellent in 33 eyes (19%), acceptable in 112 eyes (67%), poor in 24 eyes (14%), and unusable in 0 eyes (0%). Macular edema was present in 60% of eyes and was bilateral in 82% of infants with edema. At the fovea, retinal and inner nuclear layer thickness increased with edema severity: 183 ± 36 μm and 51 ± 27 μm in mild (16% of eyes), 308 ± 57 μm and 163 ± 53 μm in moderate (25%), and 460 ± 76 μm and 280 ± 83 μm in severe edema (12%), respectively. With an increase in ROP stage from 0 to 2, the mean ± standard deviation retinal thickness at the fovea increased from 227± 124 μm to 297 ± 99 μm (P < 0.001). The choroid was thinner, 155 ± 72 μm, with preplus or plus disease versus without, 236 ± 79 μm (P= 0.04), whereas retinal thickness did not vary. We demonstrated the reliability of methods and the prevalence of OCT findings in preterm infants enrolled in BabySTEPS at a single time point of 36 ± 1 weeks' PMA. Variations in layer thicknesses in infants at this time point may reflect abnormalities resulting from delay in foveal development that may be impacted by macular edema, ROP, or both.

Neuroprotective Effect of Intravitreal Single-Dose Lithium Chloride after Optic Nerve Injury in Rats

ABSTRACT Objective Lithium is an old drug to control bipolar disorder. Moreover, it presents neuroprotective effects and supports neuronal plasticity. The aim of this study was to evaluate neuroprotective effect of intravitreal lithium after optic nerve injury. Methods Three dosages of lithium chloride, including 2 pmol, 200 pmol, and 2 nmol, were injected intravitreally after rat optic nerve injury. Proteins expression were assessed by western blot. Nitric oxide (NO) metabolites were measured by Griess test. Visual evoked potential (VEP) and optical coherence tomography (OCT) measurement were performed after trauma induction, in addition to H & E and TUJ1 staining of ganglion cells. Results Western blot depicted lithium can significantly increase antiapoptotic Bcl-2 protein level and reduce p-ERK, Toll-like receptor 4 (TLR4) and proapoptotic proteins such as Bax level in retinal tissue and Griess test reflected that NO metabolites level decreased in lithium treated eyes (P < .05). While, OCT showed no significant changes (P = .36 and P = .43 comparing treated group with trauma) in retinal ganglion cell layer thickness after lithium injection, VEP P2 wave amplitude increased significantly (P < .01) in lithium-treated eyes and its latency reduced (P < .05 for N1 wave and P < .01 for P2 wave). Tuj1 antibody-labeled retinal ganglion cells analyzing showed that the number of retinal ganglion cells were significantly higher in lithium treated eyes compared to untreated eyes with optic nerve injury. Conclusion It seems intravitreally lithium has optic nerve neuroprotective effects by various mechanisms like overexpression of antiapoptotic proteins, suppressing proinflammatory molecules and proapoptotic factors, and decreasing nitric oxide.

AAV-Delivered Tulp1 Supplementation Therapy Targeting Photoreceptors Provides Minimal Benefit in Tulp1-/- Retinas.

With marketing approval of the first ocular gene therapy, and other gene therapies in clinical trial, treatments for inherited retinal degenerations (IRDs) have become a reality. Biallelic mutations in the tubby like protein 1 gene (TULP1) are causative of IRDs in humans; a mouse knock-out model (Tulp1−/−) is characterized by a similar disease phenotype. We developed a Tulp1 supplementation therapy for Tulp1−/− mice. Utilizing subretinal AAV2/5 delivery at postnatal day (p)2–3 and rhodopsin-kinase promoter (GRK1P) we targeted Tulp1 to photoreceptor cells exploring three doses, 2.2E9, 3.7E8, and 1.2E8 vgs. Tulp1 mRNA and TULP1 protein were assessed by RT-qPCR, western blot and immunocytochemistry, and visual function by electroretinography. Our results indicate that TULP1 was expressed in photoreceptors; achieved levels of Tulp1 mRNA and protein were similar to wild type levels at p20. However, the thickness of the outer nuclear layer (ONL) did not improve in treated Tulp1−/− mice. There was a small and transient electroretinography benefit in the treated retinas at 4 weeks of age (not observed by 6 weeks) when using 3.7E8 vg dose. Dark-adapted mixed rod and cone a- and b-wave amplitudes were 24.3 ± 13.5 μV and 52.2 ± 31.7 μV in treated Tulp1−/− mice, which were significantly different (p < 0.001, t-test), from those detected in untreated eyes (7.1 ± 7.0 μV and 9.4 ± 15.1 μV, respectively). Our results indicate that Tulp1 supplementation in photoreceptors may not be sufficient to provide robust benefit in Tulp1−/− mice. As such, further studies are required to fine tune the Tulp1 supplementation therapy, which, in principle, should rescue the Tulp1−/− phenotype.

P2X7 receptor antagonism preserves retinal ganglion cells in glaucomatous mice

To investigate the role of P2X7 receptor to preserve retinal ganglion cells (RGCs) structure and function in a genetic mouse model (DBA/2J mouse) of age-related glaucomatous neurodegeneration. Chronic treatment with P2X7 receptor antagonist eye drops was carried out in order to assess RGCs function and density by pattern electroretinogram (PERG) and RBPMS immunostaining, respectively. Further, microglia activation was assessed in flat-mounted retina by using Iba-1 immunostaining. Untreated glaucomatous eyes displayed significant microglia activation, alteration of PERG signal, and RGCs loss. In the P2X7 receptor antagonist-treated eyes, the PERG signal was significantly (p < 0.05) improved compared to controls, along with a significant (p < 0.05) reduction in terms of retinal microglial activation, and remarkable preservation of RGCs density. Altogether, these findings demonstrated that topical treatment with a P2X7 receptor antagonist has a neuroprotective effect on RGCs in glaucomatous mice, suggesting an appealing pharmacological approach to prevent retinal degenerative damage in optic neuropathy.

Quantifying Subclinical and Longitudinal Microvascular Changes Following Episcleral Plaque Brachytherapy Using Spectral Domain-Optical Coherence Tomography Angiography.

To assess longitudinal microvascular changes in eyes treated with I-125 episcleral plaque brachytherapy (EPB). High resolution OCT angiograms of the central 3×3mm macula were obtained from I-125 episcleral plaque brachytherapy treated and untreated fellow eyes of 61 patients. Capillary density (vessel skeleton density, VSD) and caliber (vessel diameter index, VDI) were quantified using previously validated semi-automated algorithms. Nonperfusion was also quantified as flow impairment regions (FIR). Exams from treated and fellow eyes obtained pre-treatment and at 6-month, 1-year, and 2-year intervals were compared using generalized estimating equation linear models. Dosimetry maps were used to evaluate spatial correlation between radiation dose and microvascular metrics. At 6 months, treated eyes had significantly lower VSD (0.145 ± 0.003 vs 0.155 ± 0.002; p = 0.009) and higher FIR (2.01 ± 0.199 vs 1.46 ± 0.104; p = 0.010) compared to fellow eyes. There was a significant decrease in VSD and a corresponding increase in FIR even for treated eyes without clinically identifiable retinopathy at 6 months. VDI was significantly higher in treated eyes than in fellow eyes at 2 years (2.92 ± 0.025 vs 2.84 ± 0.018; p < 0.001). When our cohort was categorized into low dose radiation (<15Gy) and high dose radiation (>45Gy) to the fovea, there were significant differences in VSD and FIR between groups. OCTA can be used to quantify and monitor EPB induced retinopathy, and can detect vascular abnormalities even in the absence of clinically observable retinopathy. OCTA may therefore be useful in investigating treatment interventions that aim to delay EPB-induced radiation retinopathy.

One-Year Functional and Anatomical Outcomes After Selective Retina Therapy With Real-Time Feedback-Controlled Dosimetry in Patients With Intermediate Age-Related Macular Degeneration: A Pilot Study.

This pilot study sought to evaluate changes in macular function and drusen volume (DV) after selective retina therapy (SRT) in patients with intermediate age-related macular degeneration (iAMD). Twenty participants with bilateral iAMD were included in this prospective interventional case series study. After titrating pulse energy by real-time feedback-controlled dosimetry, SRT with a wavelength of 527 nm was applied around the macula of one eye of each patient. Changes in best-corrected visual acuity (BCVA), DV within the central 5-mm ring (C5), and retinal sensitivity (RS) of the SRT-treated eyes (treated eyes) and untreated fellow eyes (untreated eyes) were evaluated at baseline and then at 3, 6, 9, and 12 months after treatment using linear mixed models. The mean BCVA did not change significantly between baseline and 12 months in both treated and untreated eyes (P = 0.06, P = 0.24, respectively), whereas the BCVA increase rate was faster for treated than for untreated eyes at the 12-month visit (-0.072 logMAR; 95% confidence interval [CI], -0.085 to -0.059 logMAR; P = 0.006). The mean cube root transformation of DV (cube root DV) within C5 in the untreated eyes increased significantly from 0.278 ± 0.115 at baseline to 0.295 ± 0.132 mm (P = 0.027) at 12 months, whereas the cube root DV change in treated eyes was not significant (P = 0.553). The rate of increase in the cube root DV was lower in treated than in untreated eyes at the 12-month visit (-0.016 mm; 95% CI, -0.018 to -0.011 mm; P = 0.015). The mean RS was increased from 22.49 ± 2.40 dB to 24.09 ± 2.19 dB (P < 0.001) in the treated eyes, whereas the change of mean RS in the untreated eyes was not significant at the 12-month visit (P = 0.18). The treated eyes had a higher rate of increase in RS than untreated eyes at the 12-month visit (1.012 dB; 95% CI, 0.776-1.251 dB; P = 0.037). The RS change was significantly associated with the interaction between SRT treatment and time (P = 0.028), whereas it was not associated with cube root DV change (P = 0.106). No SRT-related adverse effects were observed in all participants during the 1-year follow-up. Since SRT improved the mean RS and reduced the rate of change in drusen load in the treated eyes, as compared to the untreated eyes, SRT might slow the progression of iAMD. However, further large randomized clinical trials are necessary to confirm the efficacy of SRT for iAMD. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Chick Eyes Can Recover from Lens Compensation without Visual Cues

This study shows that nonvisual mechanism(s) can guide chick eyes to recover from myopia or hyperopia bidirectionally to regain their age-matched length. Because eye growth control is phylogenetically conserved across many species, it is possible that, in general, emmetropization mechanisms are not exclusively based on a local visual feedback system. Across species, growing eyes compensate for imposed defocus by modifying their growth, showing the visual controls on eye growth and emmetropization. When the spectacle lens is removed, the eyes rapidly recover back to a normal size similar to that in the untreated eyes. We asked whether this recovery process was dependent on visual feedback or whether it might be guided by intrinsic nonvisual mechanisms. Chicks wore either a +7 (n = 16) or -7 D (n = 16) lens over one eye for 4 to 7 days; the fellow eye was left untreated. After lens removal, half were recovered in darkness and half in white light. Refractive error and ocular dimensions were measured before and after lens treatment and after recovery with a Hartinger refractometer and A-scan biometer, respectively. Whereas chick eyes completely recovered from prior lens treatment under normal light after 2 days, they also partially recovered from prior hyperopia (by 60%) and myopia (by 69%) after being kept in darkness for 3 days: a +7 and -7 D lens induced a difference between the eyes of +7.08 and -4.69 D, respectively. After recovery in darkness, the eyes recovered by 3.18 and 2.88 D, respectively. In the absence of visual cues, anisometropic eyes can modify and reverse their growth to regain a similar length to their fellow untreated eye. Because eye growth control is phylogenetically conserved across many species, it is possible that nonvisual mechanisms may contribute more generally to emmetropization and that recovery from anisometropic refractive errors may not be wholly visually controlled.

Inner retinal layers’ alterations and microvasculature changes after vitrectomy for rhegmatogenous retinal detachment

To examine the retinal layers' changes and alterations in retinal microvasculature in patients with rhegmatogenous retinal detachment (RRD) treated with pars plana vitrectomy (PPV). Participants in this study were 103 patients with RRD, 85 macula off and 18 macula on, who were treated with PPV and gas tamponade without internal limiting membrane peeling, in two centers. All participants underwent best corrected visual acuity measurement, slit-lamp examination, fundoscopy, spectral domain-optical coherence tomography and optical coherence tomography angiography at week 5 and at month 6 postoperatively. The fellow untreated eyes were also examined and served as control data. A statistically significant enlargement in foveal avascular zone (FAZ) in both superficial capillary plexus (SCP) and deep capillary plexus (DCP) was noticed 5weeks postoperatively in patients with RRD treated with PPV compared to the fellow eyes and remained 6months after surgery. The FAZ enlargement in the operated eyes was accompanied with a statistically significant thinning of the inner retinal layer. In addition, there was a significant decrease in foveal and parafoveal vessel density (VD) in both SCP and DCP in the operated eyes compared to control eyes at week 5 postoperatively, which also remained at postoperative month 6. The study demonstrated that patients with RRD treated with PPV presented changes in the retinal microvasculature in both SCP and DCP, including enlargement of FAZ and decrease in VD. These changes seemed to be associated with inner retinal layer thinning.

Macula service evaluation and assessing priorities for anti-VEGF treatment in the light of COVID-19.

PurposeTo assess the treatment position of all patients who have had an anti-VEGF injection in 2020, prior to the UK lockdown on 23 March. To assess methods of service quality evaluation in setting benchmarks for comparison after the situation stabilized. To consider what proportion could be delayed based on national guidelines and varying vision parameters. Finally, to measure how many patients actually attended.MethodA retrospective analysis of data collected from our electronic medical record was performed. Age, sex, reason for injection, visual acuity (VA) for both treated and untreated eyes and number of injections were recorded. The proportion of patients and eyes with ≥ 70 letters were calculated as an assessment of quality of service provision. The proportion of patients that could be delayed was estimated based on published guidelines and varying the parameters of difference between treated and untreated eyes. Finally, the number of patients who actually attended was recorded.ResultsAbout 3364 eyes (2229 neovascular age-related macular degeneration (nAMD), 427 diabetic macular oedema (DMO), 599 retinal vein occlusion (RVO) and 109 other) from 2924 patients were analysed. At the last appointment with injection, 64.4% of patients achieved ≥ 70 letters in their better-seeing eye. Mean VA of the treated eye was 61.5 letters, and 36.9% achieved ≥ 70. The mean number of injections was 16, 90% with aflibercept. Of the patients receiving treatment to one eye, 57.6% was receiving treatment to their worse seeing eye. In 18.2% this eye was > 20 letters worse and in 5.07% > 40 letters worse than the untreated eye. Using Royal College of Ophthalmologists (RCOphth) guidelines, (treat nAMD 8 weekly, delay majority of RVO and DMO) 24.8% would be delayed. From 2738 appointments during the first 4 weeks of lockdown (booked prior to lockdown), doctors rescheduled 1025 and patients did not attend 820, leaving 893 who were seen (33%).ConclusionsAssessing the treatment position of patients prior to COVID-19 lockdown enables objective stratification for prioritization for continued treatment. If RCOphth guidelines were followed 24.8% could be delayed and if treating the worse seeing eye up to 57.6%. Many scheduled patients elected not to attend, with 67% not seen in the first 4 weeks. The impact of non-attendance and delays may be evaluated later.

Convolutional Neural Network Based on Fluorescein Angiography Images for Retinopathy of Prematurity Management.

PurposeThe purpose of this study was to explore the use of fluorescein angiography (FA) images in a convolutional neural network (CNN) in the management of retinopathy of prematurity (ROP).MethodsThe dataset involved a total of 835 FA images of 149 eyes (90 patients), where each eye was associated with a binary outcome (57 “untreated” eyes and 92 “treated”; 308 “untreated” images, 527 “treated”). The resolution of the images was 1600 and 1200 px in 20% of cases, whereas the remaining 80% had a resolution of 640 and 480 px. All the images were resized to 640 and 480 px before training and no other preprocessing was applied. A CNN with four convolutional layers was trained on 90% of the images (n = 752) randomly chosen. The accuracy of the prediction was assessed on the remaining 10% of images (n = 83). Keras version 2.2.0 for R with Tensorflow backend version 1.11.0 was used for the analysis.ResultsThe validation accuracy after 100 epochs was 0.88, whereas training accuracy was 0.97. The receiver operating characteristic (ROC) presented an area under the curve (AUC) of 0.91.ConclusionsOur study showed, we believe for the first time, the applicability of artificial intelligence (CNN) technology in the ROP management driven by FA. Further studies are needed to exploit different fields of applications of this technology.Translational RelevanceThis algorithm is the basis for a system that could be applied to both ROP as well as experimental oxygen induced retinopathy.

The effect of optic nerve section on form deprivation myopia in the guinea pig.

Myopia is induced when a growing eye wears a diffuser that deprives it of detailed spatial vision (form deprivation, FD). In chickens with optic nerve section (ONS), FD myopia still occurs, suggesting that the signals underlying myopia reside within the eye. As avian eyes differ from mammals, we asked whether local mechanisms also underlie FD myopia in a mammalian model. Young guinea pigs underwent either sham surgery followed by FD (SHAM + FD, n = 7); or ONS followed by FD (ONS + FD, n = 7); or ONS without FD (ONS, n = 9). FD was initiated 3 days after surgery with a diffuser that was worn on the surgically treated eye for 14 days. Animals with ONS + FD developed -8.9 D of relative myopia and elongated by 135 μm more than in their untreated eyes after 2 weeks of FD. These changes were significantly greater than those in SHAM + FD animals (-5.5 D and 40 μm of elongation after 14 days of FD), and reflected exaggerated elongation of the posterior vitreous chamber. The myopia reversed when FD was discontinued, despite ONS, but eyes did not recover back to normal (30 days after surgery, ONS + FD eyes still retained -3 D of relative myopia when SHAM+FD animals had returned to normal). No long-term residual myopia was present after ONS alone, ruling out a surgical artifact. Although the gross mechanism signaling myopic ocular growth and its recovery in the young mammalian eye does not require an intact optic nerve, its fine-tuning is disrupted by ONS.

Up-Regulation of Matrix Metalloproteinase-2 by Scleral Monocyte–Derived Macrophages Contributes to Myopia Development

Myopia is a leading cause of visual impairment worldwide. This sight-compromising condition is associated with scleral thinning, extracellular matrix remodeling, and inappropriate optical axial length elongation. Although macrophages are present in the sclera, their involvement in this condition is unknown. By using a form-deprivation myopia (FDM) mouse model, we found that both the scleral macrophage density and their matrix metalloproteinase-2 (MMP-2) expression levels increased in myopic eyes. Partial scleral macrophage depletion by clodronate shifted the refraction toward hyperopia in both the form-deprived and the untreated fellow eyes compared with their respective counterparts in the vehicle-injected control mice. However, this procedure did not alter susceptibility to FDM. FDM development was 59% less in the macrophage-specific Mmp2 deletion (LysMCreMmp-2fl/fl) mice than in their Cre-negative littermates (Mmp2fl/fl mice). Moreover, the expression of scleral C-C motif chemokine ligand-2 (CCL2), which is a potent monocyte chemoattractant recruiting monocytes to tissue sites, was increased during myopia progression. However, the increase in the density of scleral macrophages and myopia development were suppressed in fibroblast-specific Ccl2 deletion mice. These declines suggested that the increase in scleral macrophage density in myopic eyes stems from the up-regulation of scleral Ccl2 expression in fibroblasts, which, in turn, promotes monocytes recruitment. In summary, scleral monocyte-derived macrophages contribute to myopia development through enhancing MMP-2 expression in mice.

Effect of connective tissue growth factor gene editing using adeno-associated virus-mediated CRISPR-Cas9 on rabbit glaucoma filtering surgery outcomes.

Suppressing excessive wound healing responses is critical to ensure surgical success in glaucoma filtration surgery (GFS). Currently used adjunctive materials can lead to side effects due to the nonselectivity in cell inhibition and may require repeated applications. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system may become a compelling opportunity in glaucoma surgery due to its high selectivity and permanent effect. Connective tissue growth factor (CTGF) is one of the most potent stimulators of tissue fibrosis in the eye. Therefore, we tested the effect of CTGF suppression using the CRISPR-Cas9 system on GFS fibrosis. We used an adeno-associated virus (AAV)-CRISPR-Cas9 system and confirmed successful CTGF suppression was achieved in fibroblasts in vitro through western blot analysis and deep sequencing. In the in vivo intereye-comparison rabbit GFS model, CRISPR-CTGF-treated eyes showed significantly better survival of the surgery site, less subconjunctival fibrosis, limited collagen deposition, and reduced cellularity than untreated eyes. Our results suggest a new possibility of CRISPR-Cas9-mediated CTGF suppression to improve human GFS outcomes.

Effects of topical administration of tafluprost and combination of tafluprost and timolol or tafluprost and betaxolol on Schirmer tear test, intraocular pressure, and pupil size in clinically healthy dogs.

The aim of this study was to evaluate the effects of 0.0015% preservative-free (PF) tafluprost alone and in combination with 0.5% timolol maleate or0.5% betaxolol HCl on Schirmer tear test (STT), intraocular pressure (IOP), and pupil diameter (PD) in clinically normal dogs. Twenty-one healthy adult castrated male cross-bred dogs were used in this study. Dogs were randomly divided into three groups. The first group received one drop of (PF) tafluprost (Taf), in a randomly selected eye. The second group received one drop of (PF) tafluprost plus one drop of timolol maleate (Taf-Tim), and the last group received one drop of (PF) tafluprost plus one drop of betaxolol HCl, (Taf-Bet). In all groups, the fellow eyes were served as control and received one drop of saline as a placebo. IOP, STT, and PD measurements were performed at the baseline and every 30min for the first 2h, every 2 h for the next 10 h, and at 24h and 36h post-instillation (PI). In all groups, significant differences in IOP values were observed between treated and untreated eyes (Taf: p < 0.001, Taf-Tim: p = 0.014, Taf-Bet: p = 0.008). The maximum reduction in mean IOP after unilateral administration of Taf, Taf-Tim, and Taf-Bet was 8.3mmHg, 10.7mmHg, and 13mmHg, respectively. No significant differences in STT values were observed between treated and untreated eyes at any time points. In all groups, significant differences in PD values were observed between treated and untreated eyes in all time points except the baseline and 36h post-drug instillation (p < 0.001). Tafluprost alone or in combination with timolol and betaxolol was able to reduce intraocular pressure. The greatest effect of the drugs occurred 6 and 8h PI. The present study revealed that the combination of tafluprost/betaxolol is more potent in decreasing IOP than tafluprost alone or a combination of tafluprost/timolol in healthy dogs.

Morphological changes in intraretinal microvascular abnormalities after anti-VEGF therapy visualized on optical coherence tomography angiography

BackgroundTo examine the baseline morphological characteristics and alterations in intraretinal microvascular abnormalities (IRMAs) in response to anti-vascular endothelial growth factor (anti-VEGF) treatment, documented by optical coherence tomography angiography (OCTA) in diabetic eyes.MethodsIn this retrospective study, IRMAs were evaluated with multimodal imaging (fundus photography, fluorescein angiography, OCTA) in treatment-naïve diabetic eyes before and after anti-VEGF treatment for diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR) and compared to diabetic control eyes with similar diabetic retinopathy (DR) severity that did not receive anti-VEGF therapy. The morphological characteristics of IRMAs on enface OCTA imaging were graded by masked readers at baseline, then after anti-VEGF therapy in treated eyes or after observation in control eyes. Characterization of interval changes in an IRMA were based on the following parameters: branching, vessel caliber and area of adjacent capillary non-perfusion.ResultsThe treated group included 45 IRMA foci from 15 eyes of 11 patients, while the control group included 27 IRMA foci from 15 eyes of 14 patients. Following anti-VEGF treatment, enface OCTA demonstrated that 14 foci of IRMA (31%) demonstrated regression with normalization of appearance of the capillary bed, 20 IRMAs (44%) remained unchanged, six IRMAs (13%) progressed with enlargement or development of new IRMAs and five IRMAs (11%) demonstrated complete obliteration defined as IRMA disappearance with advancing capillary drop-out. In the control group, 17 IRMA (63%) remained stable, 8 IRMAs (29.6%) progressed and 2 experienced total obliteration (7.4%). The difference in rank order between the two groups was statistically significant (p = 0.022).ConclusionsIn eyes with DR status post anti-VEGF therapy, foci of IRMAs have a variable course demonstrating one of four possible outcomes: regression, stability, progression or complete obliteration. In contrast, none of the untreated control diabetic eyes demonstrated regression of IRMAs, consistent with known progression of DR severity in high risk eyes. Morphologic evaluation of IRMAs with OCTA may help to monitor changes in retinal blood flow as well as the response to anti-VEGF treatment.