Sex-Specific Differences in the Relationship Between Prematurity and Ocular Geometry.

Purpose: To explore differences in the relationship between gestational age (GA) and birth weight (BW) percentile and ocular geometry between males and females. Methods: The Gutenberg Prematurity Eye Study involved a prospective ophthalmic examination of adults, aged 18 to 52 years, who were born preterm or at term, in Germany. The associations between GA and BW percentile on the main outcome measures were evaluated by uni- and multivariable linear regression analyses. The main outcome measures were central corneal thickness, corneal radius, anterior chamber depth, lens thickness, posterior segment length, and central foveal thickness. Potential sex-specific differences and an effect modification by sex were analyzed. Results: This study involved 438 participants (245 females, 193 males) with an average age of 28.6 ± 8.7 years. In female participants, central foveal thickness was negatively associated with a higher GA (B = -2.99; P < 0.001). Similarly, male participants also demonstrated a negative association between central foveal thickness and GA (B = -4.27; P < 0.001). The multivariable model with effect modification revealed that the central foveal thickness was thicker with lower GA. There was an association between the effect modification of GA with sex and central foveal thickness, demonstrating a more pronounced effect of GA on central foveal thickness in male participants (B = 1.29; P = 0.04). Conclusions: This study identified a sex-specific correlation between lower GA and thicker central foveal thickness, suggesting differences in the developmental trajectory of this biometric parameter concerning GA. A thicker central foveal thickness might affect the visual acuity of individuals born preterm in adulthood, with a more pronounced impact in males and a potential predisposition to age-related diseases later in life. Sex did not influence the association of GA or BW percentile to other ocular geometric parameters.

Posterior segment manifestations of Takayasu arteritis: A narrative review.

Ocular symptoms can be the presenting manifestation of Takayasu arteritis (TA) or could be indicative of disease reactivation. A review of published literature related to posterior segment manifestations of TA by using the keywords "Takayasu arteritis," "ophthalmic manifestations," "retina," "retinopathy," "ocular," "optic nerve," and "optic neuropathy" was performed. In total, 62 case reports and 12 case series were included. The majority of the articles were from Asia (n = 47, 64%). Females outnumbered males in the ratio of 7:1. The mean age of patients was 33 years (range: 8-78 years, SD: 13.5 years). In 58% (n = 41 out of 71) cases, ocular symptoms were the presenting manifestation of the underlying disease. Hypotensive retinopathy was found in 70% of eyes, and hypertensive retinopathy was found in 27%. The mean presenting visual acuity (VA) was +1.03 logMAR (range: -0.12 to 3, SD: 1.07), and at the final follow-up was +1.02 logMAR (range: -0.12 to 3, SD 1.17). VA improved in 34% (n = 29/86), remained stable in 45% (39/86), and worsened in 21% (18/86). The mean follow-up was 9 months (range: 0.5-204, SD: 16 months).

Choroidal Morphology and Photoreceptor Activity Are Related and Affected by Myopia Development.

Purpose: The choroid is critical for the regulation of eye growth and is involved in the pathogenesis of myopia-associated ocular complications. This study explores the relationship among choroidal biometry, photoreceptor activity, and myopic growth in marmosets (Callithrix jacchus) with lens-induced myopia. Methods: A total of 34 common marmosets aged 92 to 273 days old were included in this study. Axial myopia was induced in 17 marmosets using negative soft contact lenses and 17 marmosets served as untreated controls. Cycloplegic refraction (RE) and vitreous chamber depth (VCD) were measured using autorefraction and A-scan ultrasonography, respectively. Choroidal scans were obtained using spectral-domain optical coherence tomography and binarized to calculate subfoveal choroidal thickness (ChT), total choroidal area (TCA), luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), and LA/SA. To assess photoreceptor activity, the a-wave of the full-field electroretinogram was measured. Regression models were used to investigate the relationship between outcome measures. Results: Eyes induced with axial myopia (RE = -7.14 ± 4.03 diopters [D], VCD = 6.86 ± 0.39 mm) showed significant reductions (4.92-21.24%) in all choroidal parameters (ChT, TCA, LA, SA, CVI, and LA/SA) compared to controls (RE = -1.25 ± 0.60 D, VCD = 6.58 ± 0.26 mm, all P < 0.05), which changed as a function of refraction and vitreous elongation, and were associated with a decrease in the a-wave amplitude. Further, multiple regression showed that a combination of ChT and CVI could well predict RE and VCD. Conclusions: This study reports the existence of significant alterations in choroidal morphology in non-human primate eyes induced with myopia. The changes in choroidal anatomy were associated with reduced light-adapted a-wave amplitude. These findings may represent early markers for reduced visual performance and chorioretinal complications known to occur in eyes with large degrees of myopia.

Spontaneously Myopic Guinea Pig: Model of Early Pathologic Myopia.

Purpose: To evaluate whether pigmented guinea pigs with spontaneous myopia present characteristic changes of pathologic myopia. Methods: The fundus images of guinea pigs (3 weeks old) were graded according to fundus tessellation (FT) degree. Biometric parameters, including refraction, vitreous chamber depth (VCD), and axial length (AL), were measured at ages 21 and 43 days. Some of these animals were divided into three groups: hyperopic without FT (H w/o FT), myopic without FT (M w/o FT), and myopic with FT (M w/ FT). The horizontal and vertical radii of curvature of posterior sclera (RP-H and RP-V, respectively) and the radii of curvature and arc lengths of superior sclera (RS and LS, respectively), inferior sclera (RI and LI, respectively), nasal sclera (RN and LN, respectively), and temporal sclera (RT and LT) were evaluated by Fuji. Results: The fundi were graded as type A or type B (both without FT), type C (mild FT), or type D (severe FT). The prevalence of FT was correlated with myopic refraction, longer VCD, and longer AL. Eyes of M w/FT animals had shorter RP-H and RP-V, longer RS and RT, and longer LS and LT than eyes of H w/o FT or M w/o FT animals. Refractions shifted toward hyperopia in eyes lacking FT, but not in eyes having FT. The changes in VCD were consistent with the changes in refraction. This relatively myopic shift in refraction and shortening of VCD were found only in myopic eyes with FT, but not in myopic eyes without FT. Conclusions: Spontaneously myopic guinea pig eyes have a high prevalence of FT. Myopic eyes with FT presented characteristic signs of pathologic myopia.

Enhanced transscleral delivery using superficial ultrasound exposure and drug-loaded hydrogel.

This study employed superficial ultrasound exposure of good ocular safety and a drug-loaded hydrogel of long residence time to enable transscleral delivery. First, we designed an acoustic adaptor to limit the ultrasound exposure depth to 1.59 mm to protect the posterior eye segments. Then, we optimized the alginate/polyacrylamide ratio (3:7) of a dual-crosslinked hydrogel to enable ultrasound-triggered release of model drug (70-kDa fluorescein isothiocyanate-conjugated dextran). Using fluorescence imaging to quantify the drug release, we showed that the developed method resulted in enhanced transscleral delivery in both ex vivo porcine scleras (2.6-fold) and in vivo rabbit scleras (2.2-fold). We also demonstrated that the method increased the drug penetration depth to the whole thickness of the sclera. In particular, the drug release efficiency increased with increasing ultrasound exposure time (1 and 3 min) and intensity (8, 19, 36, and 61 mW/cm2). Using scanning electron microscopy, we revealed that ultrasound exposure resulted in rougher surfaces and microscale rupture of the hydrogel. Moreover, Masson staining of scleral slices showed that the integrity of the top scleral fibers was disturbed by ultrasound exposure, and this disturbance recovered 3 days later. Our work demonstrates that the developed method holds great potential for mediating ocular drug delivery.

Topical ocular delivery of nanoparticles with epoetin beta in Wistar Hannover rats.

Topical instillation of drugs targeting the posterior ocular segment is an expanding area of research. Chitosan and hyaluronic acid have remarkable mucoadhesive properties and potentially enhance pre-corneal retention time after topical instillation. Bearing this in mind, we explored the possibility of delivering epoetin beta (EPOß) to the posterior segment of the eye in a chitosan-hyaluronic acid (CS/HA-EPOß) nanoparticulate system using the topical route of administration. Complete ophthalmological examinations, electroretinography and microhematocrit evaluations were performed in Wistar Hannover (WH) rats, before and after topical administration of nanoparticles. The right eye received CS/HA-EPOß and the left eye received only empty nanocarriers (control). Animals were split into 6 groups and at designated timepoints, all animals from each group (n = 3) were euthanized and both eyes enucleated. Retinal morphology and EPOß ocular distribution were assessed, respectively, through hematoxylin and eosin (HE) and immunofluorescence staining. After topical administration, no adverse ocular signs were noted and no significant changes either in microhematocrits nor in electroretinographies were detected. During the study, intraocular pressure (IOP) was always kept within physiological range bilaterally. No histological changes were detected in any of the ocular globes. Immunofluorescence enabled the identification of EPOß in the retina 12 h after the administration, its presence still being detectable at day 21. In conclusion, CS/HA nanoparticles could efficiently deliver EPOß to the retina of WH rats after topical instillation, being considered biologically safe. Topical administration of this nanoformulation could be a valuable tool for retinal neuroprotection, decreasing risks associated with more invasive routes of administration, being cost effective and also increasing long-term patients' compliance.

The topical ocular delivery of rapamycin to posterior eye tissues and the suppression of retinal inflammatory disease.

Treatment of posterior eye diseases with intravitreal injections of drugs, while effective, is invasive and associated with side effects such as retinal detachment and endophthalmitis. In this work, we have formulated a model compound, rapamycin (RAP), in nanoparticle-based eye drops and evaluated the delivery of RAP to the posterior eye tissues in a healthy rabbit. We have also studied the formulation in experimental autoimmune uveitis (EAU) mouse model with retinal inflammation. Aqueous RAP eye drops were prepared using N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (Molecular Envelope Technology - MET) containing 0.23 ± 0.001% w/v RAP with viscosity, osmolarity, and pH within the ocular comfort range, and the formulation (MET-RAP) was stable in terms of drug content at both refrigeration and room temperature for one month. The MET-RAP eye drops delivered RAP to the choroid-retina with a Cmax of 145 ± 49 ng/g (tmax = 1 h). The topical application of the MET-RAP eye drops to the EAU mouse model resulted in significant disease suppression compared to controls, with activity similar to dexamethasone eye drops. The MET-RAP eye drops also resulted in a reduction of RORγt and an increase in both Foxp3 expression and IL-10 secretion, indicating a mechanism involving the inhibition of Th17 cells and the up-regulation of T-reg cells. The MET-RAP formulation delivers RAP to the posterior eye segments, and the formulation is active in EAU.

Study of the Correlation Between Severity of Endophthalmitis and Posterior Vitreous Detachment Using a Rabbit Endophthalmitis Model.

Purpose: We have reported that the absence of posterior vitreous detachment (PVD) is related to the onset and severity of infectious endophthalmitis, based on clinical experience. To demonstrate clinical findings in animal models, we created endophthalmitis models for the presence or absence of PVD and examined differences in severity. Method: We estimated a rabbit infectious eye model with and without PVD using Pseudomonas aeruginosa (PVD(+) and PVD(-) groups). After injection of bacteria inoculation for 3, 6, 12, and 24 hours, we evaluated the clinical score of the anterior chamber (n = 14). Removing the vitreous and retina from the enucleated eyeballs, the number of bacteria was counted using each specimen (n = 12). In addition, the number of inflammatory cells approximately 3 mm2 around the optic disc and histopathologic grading of intraocular inflammation was compared from histopathologic images (n = 7). Electroretinogram (ERG) was performed in experimentally infected rabbit eyes in both groups at three times after injection of the bacterial suspension. Results: There was no difference between the two groups in the clinical score of the anterior chamber of each time phase, but the bacterial cultures showed significantly fewer bacteria in the PVD(-) group 24 hours after bacterial inoculation (P < 0.05). Furthermore, the number of inflammatory cells was significantly less in the PVD group (P < 0.05). As a result of ERG, the decreases of a- and b-waves in amplitude were significantly greater in the PVD(-) group than in the PVD(+) group. Conclusions: The present study confirms using animal models that the absence of PVD contributed to the severity of bacterial endophthalmitis.

LOW VULNERABILITY OF THE POSTERIOR EYE SEGMENT TO SARS-COV-2 INFECTION: Chorioretinal SARS-CoV-2 Vulnerability.

PURPOSE: Retinal manifestations have been described in COVID-19 patients, but it is unknown whether SARS-CoV-2, the causal agent in COVID-19, can directly infect posterior ocular tissues. Here, we investigate SARS-CoV-2 host factor gene expression levels and their distribution across retinal and choroidal cell types. METHODS: Query of single-cell RNA sequencing data from human retina and choroid. RESULTS: We find no relevant expression of two key genes involved in SARS-CoV-2 entry, ACE2 and TMPRSS2, in retinal cell types. By contrast, scarce expression levels could be detected in choroidal vascular cells. CONCLUSION: Given the current understanding of viral host cell entry, these findings suggest a low vulnerability of the posterior eye segment to SARS-CoV-2 with a potential weak spot in the vasculature, which could play a putative causative role in ocular lesions in COVID-19 patients. This may qualify the vasculature of the human posterior eye segment as an in vivo biomarker for life-threatening vascular occlusions in COVID-19 patients.

Posterior segment findings by spectral-domain optical coherence tomography and clinical associations in active toxoplasmic retinochoroiditis.

Toxoplasmic retinochoroiditis is a common, potentially blinding parasitic infection. We sought to define the spectrum and frequency of signs of active toxoplasmic retinochoroiditis by spectral domain optical coherence tomography (SD-OCT), and to identify clinical associations. Ninety eyes of 90 individuals presenting consecutively to a tertiary referral uveitis service with active toxoplasmic retinochoroiditis and gradable SD-OCT scans were evaluated prospectively. SD-OCT features were collated, and associations with lesion location, primary versus recurrent episode, serological status, human immunodeficiency virus infection and best-corrected Snellen visual acuity were explored. Active toxoplasmic retinochoroiditis presented with thickened (65%) and hyperreflective (61%) retina, choroidal thickening (55%) and hyporeflectivity (61%), hyperreflective vitreous dots (80%) and deposits (36%), and posterior hyaloid thickening (35%) on SD-OCT. Most signs occurred with similar frequency across clinical groups. Retinal hyporeflectivity (17%) was significantly associated with a visual acuity of 20/200 or worse at resolution. Our observations demonstrate that active toxoplasmic retinochoroiditis has diverse SD-OCT signs and that none are universally present. Retinal hyporeflectivity-suggesting liquefactive necrosis-predicts poor visual outcome.

Aqueous eye drops containing drug/cyclodextrin nanoparticles deliver therapeutic drug concentrations to both anterior and posterior segment.

Using topical application to deliver therapeutic concentrations of drugs to the posterior segment of the eye remains very challenging. As a result, posterior segment diseases are usually treated by intravitreal injection or implant. While topical treatments are commonly used for anterior segment conditions, they sometimes require frequent applications. Eye drop formulations based on γ-cyclodextrin (γCD)-based nanoparticle aggregates were developed, which in animal models and clinical studies deliver therapeutic concentrations of drugs (dorzolamide and dexamethasone) to both anterior and posterior segments of the eye. An early study in humans showed dorzolamide/γCD eye drops could achieve comparable intraocular pressure decreases to commercial dorzolamide eye drops, but with less frequent application. Pilot studies with dexamethasone/γCD eye drops suggested that they could be effective in a range of conditions, including diabetic macular oedema, cystoid macular oedema and vitritis secondary to uveitis, postcataract surgery inflammation and postoperative treatment in trabeculectomy. Phase II studies with similar dexamethasone/γCD nanoparticle eye drops in diabetic macular oedema and postcataract surgery inflammation have recently been completed. This technology has the potential to be used with other classes of drug molecules and to replace or complement invasive treatments, providing safer, non-invasive therapies, particularly for posterior segment conditions, that can be self-administered as eye drops by patients.

Development and optimization of Riluzole-loaded biodegradable nanoparticles incorporated in a mucoadhesive in situ gel for the posterior eye segment.

Riluzole-loaded PLGA nanoparticles (RLZ-NPs) were developed to improve the biopharmaceutical profile of RLZ after ocular administration. Moreover, RLZ-NPs were dispersed in an in situ gelling system (RLZ-NPs-Gel) for topical administration as a potential neuroprotective strategy against glaucoma. Formulations were optimized using the design of experiments approach. Characterization of the physicochemical and rheological properties, as well as interaction studies were carried out. To ensure RLZ-NPs-Gel ocular safety, the irritant potential was also evaluated in vitro and in vivo. Moreover, in vivo ocular biodistribution was also undertaken. Optimized RLZ-NPs showed an average size below 200 nm, an encapsulation efficiency greater than 90% and a negative surface charge. Interaction studies of RLZ-NPs showed that RLZ was dispersed in the polymeric matrix. RLZ-NPs-Gel possess a pseudoplastic behavior and a medium-low post-gelling viscosity to avoid discomfort after ocular application. Simultaneously, RLZ-NPs-Gel were able to increase RLZ-NPs contact with the ocular surface. Both formulations demonstrated the ability to be distributed in the posterior eye segment after 24 h of their application obtaining a more delayed distribution for RLZ-NPs-Gel. Therefore, a novel in situ gelling system able to disperse RLZ-NPs has been successfully developed as innovative neuroprotective strategy for potential topical treatment of glaucoma.

OPTICAL COHERENCE TOMOGRAPHIC PATTERNS OF POSTERIOR SEGMENT STICKY HEAVY SILICONE OIL.

PURPOSE: To describe unique optical coherence tomography observations of adherent preretinal heavy silicone oil after removal. METHODS: Retrospective observational review of files and optical coherence tomography scans of patients who had pars plana vitrectomy with heavy silicone oil. We investigated the possible precipitating preoperative and intraoperative factors and the association with postoperative epiretinal membrane and cystoid macular edema. RESULTS: Forty-one eyes from 39 patients were involved. Two characteristic sticky silicone oil structures were identified in 33 patients (80%): variably reflective macrodroplets (bubbles) and hyperreflective microdroplets (dots). The main contributing variable was the tamponade duration. Other notable associations included postoperative epiretinal membrane and cystoid macular edema formation. Surgical interventions including heavy liquid did not show a strong predilection to their development. We reported two novel findings of sticky prefoveal macrodroplets in five patients and intravitreal macrodroplets and microdroplets casting shadows on the underlying retina in four patients. CONCLUSION: This study confirms previously reported optical coherence tomography observations of sticky emulsified silicone oil remnants after removal. This is the first report of two distinctly different optical coherence tomography appearances after heavy silicone oil removal. The variability in size and reflectivity may be attributed to the amount and nature of the induced inflammatory reaction.

Lipid Nanoparticles Traverse Non-Corneal Path to Reach the Posterior Eye Segment: In Vivo Evidence.

Lipid-based nanocarriers (LNs) have made it possible to prolong corneal residence time and improve the ocular bioavailability of ophthalmic drugs. In order to investigate how the LNs interact with the ocular mucosa and reach the posterior eye segment, we have formulated lipid nanocarriers that were designed to bear a traceable fluorescent probe in the present work. The chosen fluorescent probe was obtained by a conjugation reaction between fluoresceinamine and the solid lipid excipient stearic acid, forming a chemically synthesized adduct (ODAF, N-(3',6'-dihydroxy-3-oxospiro [isobenzofuran-1(3H),9'-[9H] xanthen]-5-yl)-octadecanamide). The novel formulation (LN-ODAF) has been formulated and characterized in terms of its technological parameters (polydispersity index, mean particle size and zeta potential), while an in vivo study was carried out to assess the ability of LN-ODAF to diffuse through different ocular compartments. LN-ODAF were in nanometric range (112.7 nm ± 0.4), showing a good homogeneity and long-term stability. A TEM (transmission electron microscopy) study corroborated these results of characterization. In vivo results pointed out that after ocular instillation, LN ODAF were concentrated in the cornea (two hours), while at a longer time (from the second hour to the eighth hour), the fluorescent signals extended gradually towards the back of the eye. From the results obtained, LN-ODAF demonstrated a potential use of lipid-based nanoparticles as efficient carriers of an active pharmaceutical ingredient (API) involved in the management of retinal diseases.

Correlation of in vivo/ex vivo imaging of the posterior eye segment.

BACKGROUND: For an understanding of the pathology of retinal diseases, direct comparisons of high-resolution in vivo retinal imaging and ex vivo histological preparations are desirable. MATERIAL AND METHODS: Multimodal in vivo and ex vivo imaging of a human donor eye with secondary alterations showing atrophic retina due to central retinal arterial occlusion. The subsequent correlation with the histological examination was carried out on identical tissue localizations. RESULTS: Appropriate custom-built retinal imaging devices facilitate in vivo and ex vivo correlations and the examination of human eye tissue and acquisition of retinal images, e.g. SD-OCT. The precise alignment of the tissue enables a histological analysis on identical sites. CONCLUSION: The direct correlation of clinical in vivo imaging with ex vivo imaging including histopathology can further enhance our understanding in the pathogenesis of retinal diseases; however, the proposed method is currently limited due to restricted availability of human donor tissue.

Canonical Wnt Signaling Drives Myopia Development and Can Be Pharmacologically Modulated.

Purpose: The purpose of this study was to evaluate the role of the canonical Wnt signaling in the development of the myopia. Methods: Plasma from adult patients with myopia, myopic animal models including the adenomatous polyposis coli (APC) gene mutation mouse model, and the form deprivation (FD) induced mouse model of myopia were used. Niclosamide, a canonical Wnt pathway inhibitor, was orally administrated in animal models. Plasma levels of DKK-1 were determined by using enzyme-linked immunosorbent assay. Refraction, vitreous chamber depth (VCD), axial length (AL), and other parameters, were measured at the end of the FD treatment. Canonical Wnt signaling changes were evaluated by Western blot analysis and immunostaining analysis. Results: Plasma level of Wnt inhibitor DKK-1 was markedly decreased in patients with myopia. Meanwhile, the canonical Wnt pathway was progressively activated during myopia development in mice. Moreover, inhibition of canonical Wnt signaling by niclosamide in mouse models markedly reduced lens thickness (LT), VCD, and AL elongation, resulting in myopia inhibition. Conclusions: Dysregulation of canonical Wnt signaling is a characteristic of myopia and targeting Wnt signaling pathways has potential as a therapeutic strategy for myopia.

POSTOPERATIVE POSTERIOR SEGMENT COMPLICATIONS AFTER BOSTON TYPE 1 KERATOPROSTHESIS: Incidence, Risk Factors, and Intermediate-Term Outcomes.

PURPOSE: To identify the incidence of, risk factors for, and outcomes of posterior segment complications (PSC) after Boston Type 1 keratoprosthesis (KPro) implantation. METHODS: Retrospective, consecutive case series of KPro procedures at the Stein Eye Institute. Data regarding ocular history, intraoperative details, postoperative management, and outcomes were collected. Eyes with at least one PSC (PSC group) were compared with eyes without PSC (No PSC group), and risk factors for PSC were determined. RESULTS: Ninety-five PSC occurred in 69/169 eyes (40.8%), at a mean of 20.1 months after KPro implantation (0.01 complications/eye month). The median follow-up after KPro implantation was 44.0 months (range 3.0-174.4). The most common PSC were epiretinal membrane (16.6%), cystoid macular edema (12.4%), vitritis (11.2%), and retinal detachment (9.5%). Previous retinal detachment repair, concomitant intraocular lens removal, postoperative aphakia, and vitritis were risk factors for retinal detachment. Postoperative infectious keratitis was a risk factor for epiretinal membrane, cystoid macular edema, and vitritis. The posterior segment complication group had a significantly higher rate of eyes failing to maintain visual acuity ≥20/200 (HR = 2.28; 95% CI = 1.35-3.85) and KPro retention failure rate (HR = 1.66; 95% CI = 0.95-2.91). CONCLUSION: Posterior segment complications occur in approximately 40% of eyes after KPro implantation, resulting in reduced visual outcomes and KPro retention.

Chitosan coated nanoparticles for efficient delivery of bevacizumab in the posterior ocular tissues via subconjunctival administration.

In several ocular diseases, vascular endothelial growth factor (VEGF) level has been found to be unregulated. Bevacizumab, an anti-VEGF drug, is the most commonly used off level drug for diabetic retinopathy (DR). The present study was to evaluate the chitosan-coated poly (lactide-co-glycolic acid) nanoparticles (CS-PLGA NPs) for sustained and effective delivery of bevacizumab to posterior ocular tissues. The penetration of NP through sclera was studied by confocal laser scanning microscopy (CLSM). For pharmacokinetic study, bevacizumab loaded NPs were administered into the rat eye through subconjunctival injection (SCJ) and pharmacokinetic parameters were compared to drug solution. CLSM and pharmacokinetic study showed better penetration of formulation and higher concentration of bevacizumab in posterior ocular tissues. In retinopathy model, CS-PLGA NPs by SCJ route showed more reduction of VEGF level in retina than the topical and intravitreal administration of formulation. Thus, CS-coated PLGA NPs can be potentially useful as carriers to target retina.

Intraocular pressure and injection forces during intravitreal injection into enucleated porcine eyes.

Injection of biological molecules into the intravitreous humor is of increasing interest for the treatment of posterior segment eye diseases such as age-related degenerative macular degeneration. The injection volume is limited by an increase in intraocular pressure (IOP) and 50-100 µL are typically used for most intravitreally (IVT) applied commercial products. Direct measurement of IOP is difficult and has not been studied dependent on solution properties and injection rates. We used an instrumental set-up to study IOP ex vivo using healthy enucleated porcine eyes. IOP was determined as a function of injection volume for viscosities between 1 and 100 mPas, injection rates of 0.1, 1, and 1.5 mL/min, and needle length and diameter (27/30G and 0.5/0.75″) using Dextran solutions. IOP increased exponentially for injection volumes larger than 100 µL. We did not observe differences in IOP dependent on viscosity, injection rate, and needle diameter. However, variability increased significantly for injection volumes larger than 100 µL and, unexpectedly, declined with higher viscosities. We demonstrate that the exponential increase in IOP is not reflected by injection force measurements for typical configurations that are used for IVT application. The present findings may guide injection volumes for intravitreal injection and inform injection force considerations during technical drug product development.