Downie,L. E., Craig,J. P., Stapleton,F., Tan,J., Jones,L., Ng, A.Y., Hinds,M., Bosworth,C., Alster,Y. Efficacy and safety of AZR-MD-001 selenium sulfide ophthalmic ointment in adults with meibomian gland dysfunction over six months of treatment: A Phase 2, vehicle-controlled, randomized extension trial Ocular Surface 2025;35(January):15-24 [ Show Abstract ]

Purpose: To determine the efficacy and safety of AZR-MD-001 (0.5 % and 1.0 %) ophthalmic ointment, relative to vehicle, over 3–6 months of treatment, in participants with meibomian gland dysfunction (MGD).

Methods: This was a Phase 2, randomized, vehicle-controlled, multicenter extension clinical trial. Eligible participants were adults with MGD (meibomian gland secretion score (MGS) ≤12 out of 15 glands) who discontinued all other dry eye or MGD treatments. Participants were randomized 1:1:1 to apply AZR-MD-001 1.0 %, 0.5 %, or vehicle to the lower eyelids, twice weekly. Key exploratory endpoints included the least-squared mean difference between groups in the change from baseline in clinical signs (meibomian gland yielding score; MGYLS) and symptoms (Ocular Surface Disease Index; OSDI), at clinic visits at Month 4.5 and 6, and safety measures from 36 months.

Results: Participants (66.5 % female) were randomized, at baseline, to AZR-MD-001 0.5 % (n = 82), 1.0 % (n = 83), or vehicle (n = 80). Statistically significant improvements, compared to vehicle, were observed at Month 6 in MGYLS for both AZR-MD-001 groups (0.5 % group: 1.9, 95 % CI 0.9 to 2.8, P = 0.002; 1.0 % group: 1.1, 95 % CI 0.2 to 2.1, P = 0.026), and in OSDI score for the 0.5 % group (−4.5, 95 % CI -8.0 to −0.9, P = 0.0135). The most common adverse events for AZR-MD-001 were application site pain, superficial punctate keratitis and eye pain; most were mild to moderate in severity, and decreased in incidence over time.

Conclusions: AZR-MD-001 (0.5 %) was efficacious in treating signs and symptoms of MGD over six months, with a lower observed incidence of new adverse events over time.

Garg,P., Shokrollahi,P., Darge,H., Phan,C-M., Jones,L. Controlled PVA Release from Chemical-Physical Interpenetrating Networks to Treat Dry Eyes ACS Omega 2025;10(1):1249-1260

Garg,P., Shokrollahi,P., Darge,H., Phan,C-M., Jones,L. 3D-Printed Contact Lenses to Release Polyvinyl Alcohol as a Therapeutic Agent for the Treatment of Dry Eyes Pharmaceutics 2025;17(2):219 [ Show Abstract ]

Purpose: Dry eye disease is highly prevalent, and the most common treatment, lubricating eye drops, only remains effective for a very short period of time. This project aims to 3D print a proof-of-concept, custom-fit, polyvinyl alcohol (PVA)-eluting contact lens (CL) for the treatment of dry eye disease. PVA is a commonly used viscosity enhancer in eye drops, with the capability of reducing symptoms of dry eye by stabilizing the tear film and reducing tear evaporation. The protective effects of PVA could be attributed to its water-retaining ability, which provides moisturization and prevents the loss of water.

Method: In this work, a low-cost stereolithography-based 3D printer was retrofitted with a humidity and temperature control kit to 3D print a PVA-loaded custom-fit CL. To evaluate the print quality of the 3D-printed CL, circularity was used to evaluate the shape fidelity in 3D printing. The PVA release from these lenses was assessed, along with its role in acting as a viscosity enhancer. The effect of PVA was further analyzed by a dry eye disease (desiccation stress) cell model.

Results: The shape fidelity evaluation of the 3D-printed CL displayed excellent circularity. The diameter, sagittal depth, and base curve of the 3D-printed lenses were measured to be 14.27 ± 0.06 mm, 3.77 ± 0.16 mm, and 6.4 ± 0.24 mm, respectively. The PVA release curves showed that approximately 1300 µg of PVA was released over the study duration of 24 h.

Conclusions: Overall, this work demonstrates that a 3D-printed PVA-eluting CL is a promising candidate for the treatment of dry eye.

Garg,P., Shokrollahi,P., Phan,C.-M., Jones,L. Biodegradable 3D-Printed Conjunctival Inserts for the Treatment of Dry Eyes
Polymers 2025;17(5): [ Show Abstract ]

Purpose: To fabricate 3D-printed, biodegradable conjunctival gelatin methacrylate (GelMA) inserts that can release polyvinyl alcohol (PVA) when exposed to an ocular surface enzyme.

Method: In this work, biodegradable conjunctival inserts were 3D-printed using a stereolithography-based technique. The release of PVA from these insert formulations (containing 10% GelMA and 5% PVA (P-Gel-5%)) was assessed along with different mathematical models of drug release. The biodegradation rates of these inserts were studied in the presence of a tear-film enzyme (matrix metalloproteinase-9; MMP9). The morphology of the inserts before and after enzymatic degradation was monitored using scanning electron microscopy.

Results: The 3D-printed P-Gel-5% inserts formed a semi-interpenetrating network, which was mechanically stronger than GelMA inserts. The PVA release graphs demonstrate that at the end of 24 h, 222.7 ± 20.3 µg, 265.5 ± 27.1 µg, and 242.7 ± 30.4 µg of PVA were released when exposed to 25, 50, and 100 µg/mL of MMP9, respectively. The release profiles of the P-Gel-5% containing hydrogels in the presence of different concentrations of MMP9 showed the highest linearity with the Korsmeyer–Peppas model. The results suggest that the degradation rate over 24 h is a function of MMP9 enzyme concentration. Over 80% of P-Gel-5% inserts were degraded at the end of 8 h, 12 h, and 24 h in the presence of 100, 50, and 25 µg/mL MMP9 enzyme solutions, respectively.

Conclusions: These results demonstrate the potential for 3D printing of GelMA for use as conjunctival inserts. These inserts could be used to deliver PVA, which is a well-known therapeutic agent for dry eye disease. PVA release is influenced by multiple mechanisms, including diffusion and enzymatic degradation, which is supported by morphological studies and biodegradation results.

Jiang,Q., Zhang,Z., Niu,L., Wang,B., Fadel,D., Wei,R., Chen,Z. Changes in anterior segment after short-term scleral lens wear in healthy Chinese population Contact Lens Anterior Eye 2025;48(1):102291 [ Show Abstract ]

Purpose
To evaluate the impact of short-term scleral lens (SL) wear on anterior chamber (AC) dimension and central corneal thickness (CCT) in healthy Chinese people.

Methods
This is a prospective, daily wear study. Eligible participants were dispensed SLs to correct refractive errors. Anterior segment (AS) parameters were measured by AS optical coherence tomography (AS-OCT) before, during, and after 2 and 4 hours of lens wear. Repeated-measures analysis of variance (ANOVA) was used to analyze the changes in AS parameters over time.

Results
Twelve subjects (10 females and 2 males) with a mean age of 25.3 ± 3.8 years (ranging from 21 to 34 years) were recruited. The AC parameters, including anterior chamber depth (ACD) from the endothelium (endo-ACD), angle opening distance at 500 μm (AOD500), and trabecular-iris space area at 500 μm (TISA500), significantly decreased after wearing SLs for 4 hours (P<0.05). CCT increased by 12 μm (2.29 %) after wearing SLs for 4 hours (P=0.013).

Conclusion
This study suggests that SL wear has a significant impact on AS dimensions in patients with healthy corneas in the short term with SL in situ, but tend to recover quickly after SL removal. Further research is needed to determine whether the change in AS dimensions during SL wear affects aqueous humor (AH) outflow and causes changes in intraocular pressure (IOP).

Ngo,W., Nagaarudkumaran,N., Huynh,C. B. Refrigeration reduces instillation discomfort of a 0.09% cyclosporine A solution Optometry and Vision Science 2025;102(1):14-19 [ Show Abstract ]

Significance: Topical cyclosporine A (CsA) for the treatment of dry eye disease is often associated with instillation discomfort, which may negatively influence patient adherence to therapy. This study found that refrigerating topical CsA reduced instillation discomfort compared with instillation of warm CsA. Thus, refrigerating CsA prior to instillation may improve patient experience when using CsA to manage dry eye disease.

Purpose: This study aimed to quantify instillation discomfort associated with cold or warm instillation of a 0.09% CsA.

Methods: Forty participants with symptomatic aqueous deficient dry eye were enrolled. A drop of cold (4°C) CsA was instilled in one eye, and a drop of warm (23°C) CsA was instilled in the other eye. The order and eye receiving the cold drop were randomized. Participants rated the discomfort of each eye (0, no discomfort; 10, maximal discomfort) prior to drop instillation, immediately post-instillation, and at each subsequent minute for 10 minutes. Area under the curve was used to quantify cumulative discomfort.

Results: Forty participants (39.6 ± 18.9 years old, 82% female) completed the study. A majority of participants (n = 24, 60%) experienced reduced cumulative discomfort with cold CsA, whereas the remainder experienced minimal difference (n = 10, 25%) or increased cumulative discomfort (n = 6, 15%). For those with reduced discomfort (n = 24), cumulative discomfort associated with cold instillation (median, 11.5 [2.2, 20.0]) was significantly lower (p<0.01) than cumulative discomfort associated with warm instillation (median, 17.5 [11.2, 32.2]). Cold instillation was associated with a median reduction of 1 discomfort point immediately post-instillation and at all subsequent time points (all p≤0.04, but not significant at t = 10), compared with warm instillation.

Conclusions: Up to 60% of participants found that cold instillation of CsA solution induced less discomfort than warm instillation, lasting up to 9 minutes post-instillation. In contrast, although 15% of participants found reduced discomfort with warm instillation, the magnitude of discomfort associated with warm instillation was not significantly different than cold instillation.

Shokrollahi,P., Garg,P., Wulff,D., Hui,Al., Phan,C-M., Jones,L. Vat Photopolymerization 3D Printing Optimization: Analysis of Print Conditions and Print Quality for Complex Geometries and Ocular Applications International Journal of Pharmaceutics 2025;668(January):124999 [ Show Abstract ]

Abstract: 3D printing, also known as additive manufacturing, continues to reshape manufacturing paradigms in healthcare by providing customized on-demand object fabrication. However, stereolithography-based 3D printers encounter a conflict between optimizing printing parameters, requiring more time, and print efficiency, requiring less time. Moreover, commonly used metrics to assess shape fidelity of 3D printed hydrogel materials like ‘circularity’ and ‘printability’ are limited by the soft nature of hydrogels, that can cause irregularities in their boundary. To unlock the full potential of 3D printing of biomaterials, it is also necessary to understand correlation between printing parameters and ink properties. In this work, a method based on curing depth, overcuring (cumulative cure), and print thickness was developed, which enables a time-efficient and reliable determination of printing conditions for complex geometries using gelatin methacrylate hydrogel biomaterial ink. We also examined the impact of printing direction on the print quality in terms of object/print thickness and aspect ratio. Moreover, the effects of dye concentration, exposure time, and layer thickness on print quality were evaluated, with discussions focused on the correlation between print dimension to layer thickness. Further evaluation was achieved by successfully printing bioinspired corneal stroma-like scaffold and delicate structures like a contact lens and a model eyeball, substantially expanding the scope of this method in producing high-quality prints with intricate details. We also demonstrate the effectiveness of ‘Feret ratio,’ another measure of object shape, in assessing the shape fidelity of different prints. Overall, the results highlight the practical potential of this method in enhancing the speed and reliability of the 3D printing processes involving complex geometries using a low-cost 3D printers.