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Purpose: The purpose of the present study was to improve the ocular delivery for ketorolac tromethamine (KT) used to treat inflammation of the eye. Methods: Eudragit nanoparticles loaded with KT were prepared and incorporated in polyvinyl alcohol (PVA) and hydroxyethyl cellulose (HEC) films. Nanoparticles were characterized by Fourier transform-infrared (FT-IR), scanning electron microscopy (SEM). Physicochemical properties and encapsulation effciency were investigated for nanoparticles. Also, the inserts were evaluated for their physiochemical parameters like percentage moisture absorption, percentage moisture loss, thickness and folding endurance. Results: Mean particle size and zeta potential were in range of 153.8-217 nm and (-10.8) - (-40.7) mV, respectively. The results show that the use of a surfactant has not led to any major change on drug loading. The loading increases with the amount of polymer. The insert had a thickness varying from 0.072 ± 0.0098 to 0.0865 ± 0.0035 mm. The thicknesses of the inserts and the folding endurance increased with the total polymer concentration. The physicochemical properties showed that the Eudragit® L-100 nanoparticles loaded PVA-HEC films could be an effective carrier for KT. Conclusion: For the first time, inserts of Eudragit nanoparticles were successfully prepared for ophthalmic drug delivery system to prevent frequent drug administration and enhance patient compliance.

Pharmaceuticals delivery to the eye sites of interest via the means of contact lenses (CLs) has attracted significant research attention in recent years. Compared with the conventional formulation in eye treatment such as eye drops, CLs administration has shown remarkable advantages in overcoming the challenges involved in ocular drug delivery such as higher bioavailability, longer drug residence and better medication compliance. This review will first detail each of the material components which have been used in the context of CLs, including HEMA, MAA, DMA, NVP, EGDMA, TRIS and PDMS. The pros and cons of each material in tailoring drug release rates of different encapsulated payloads will be discussed, with special focus on their impact on the therapeutic efficiency. In addition, the advancement of recent emerging copolymer CLs hydrogels, originated from these sophisticated monomers with distinct functions, are further summarized into several synthetic strategies in the means of copolymer architecture design and function‐performance relationship in ophthalmic applications. Finally, the possible considerations for future design of multifunctional CLs hydrogels by combing material selection rationales with biological interface science are proposed. [ABSTRACT FROM AUTHOR]

Voriconazole (VRC) is a broad spectrum, second generation triazole antifungal. The main use of VRC is via the oral and intravenous route. The study aimed to formulate VRC into ternary micellar systems (TMSs) for the topical treatment of ocular mycosis. TMSs were successfully prepared by water addition/solvent evaporation method, applying a 3-factor D-optimal design. The numerical optimization process suggested an optimal formula (OTMS) composed of total Pluronics to drug weight ratio of 22.89: 1, 1:1 weight ratio of Pluronic® P123 and F68, and 2% w/v of Labrasol. OTMS had high solubilization efficiency of 98.0%, small micellar size of 21.8 nm and suitable zeta potential and polydispersity index values of -9.0 mV and 0.261, respectively. OTMS exhibited acceptable stability for 3 months. Transmission electron microscopy demonstrated the spherical morphology of micelles. OTMS was expected to cause no ocular irritation or blurring in vision as reflected by pH and refractive index measurements. The histopathological study revealed the safety of OTMS for ocular use. The fungal susceptibility testing using Candida albicans demonstrated the superiority of OTMS to VRC suspension, with greater and more durable growth inhibition. Therefore, ocular application of optimized VRC-loaded TMSs can be a promising treatment for ocular mycosis. [ABSTRACT FROM AUTHOR]

Glaucoma is a wide-spread eye disease caused by elevated intraocular pressure. Uncontrolled, this pressure may lead to damages to the optic nerve. Prostaglandin analogues, such as latanoprost and travoprost (which are water-insoluble active substances), are the most used class of active pharmaceutical ingredient. To administer them as eye drops, preservatives, such as benzalkonium chloride, are used as solubilizers. The latter is known to cause a local inflammation when used chronically and is not recommended for patients with ocular surface disorders. In this work, we sought to use polysorbate 80 (PS80) as a solubilizing agent simultaneously with sodium hyaluronate (NaHA) as a thickener and cytoprotective agent for the corneal surface. The first part of this study assessed the compatibility of the excipients with the active substance, using physicochemical methods such as spectra fluorescence and differential scanning calorimetry (DSC), as well as the solubilization mechanism of PS80 regarding prostaglandin analogues using nuclear magnetic resonance (NMR). The second part evaluated the stability of a formula candidate, its viscosity upon instillation, and its pharmacokinetic profile in rabbits as compared to the commercially approved medicine Travatan®. The results show that sodium hyaluronate is inert with respect to travoprost, while PS80 successfully solubilizes it, meaning that benzalkonium chloride is no longer required. Moreover, the pharmacokinetic profiles of the rabbits showed that the original formula described in the present study enhanced the ocular bioavailability of the drug, making it a promising product to control intraocular pressure with a potential reduced dosage of travoprost, therefore minimizing its related side effects.

The eye is the specialized part of the body and is comprised of numerous physiological ocular barriers that limit the drug absorption at the action site. Regardless of various efforts, efficient topical ophthalmic drug delivery remains unsolved, and thus, it is extremely necessary to advance the contemporary treatments of ocular disorders affecting the anterior and posterior cavities. Nowadays, the advent of nanotechnology-based multicomponent nanoemulsions for ophthalmic drug delivery has gained popularity due to the enhancement of ocular penetrability, improve bioavailability, increase solubility, and stability of lipophilic drugs. Nanoemulsions offer the sustained/controlled drug release and increase residence time which depend on viscosity, compositions, and stabilization process, etc.; hence, decrease the instillation frequency and improve patient compliance. Further, due to the nanosized of nanoemulsions, the sterilization process is easy as conventional solutions and cause no blur vision. The review aims to summarizes the various ocular barriers, manufacturing techniques, possible mechanisms to the retention and deep penetration into the eye, and appropriate excipients with their under-lying selection principles to prevent destabilization of nanoemulsions. This review also discusses the characterization parameters of ocular drug delivery to spike the interest of those contemplating a foray in this field. Here, in short, nanoemulsions are abridged with concepts to design clinically advantageous ocular drug delivery. Unlabelled Image [ABSTRACT FROM AUTHOR]

Targeted delivery of drugs at appropriate concentrations to ocular tissues is required to avoid wastage. Hence, advanced systems that maximize the release of poorly soluble drugs and deliver them at ocular sites must be designed. In this study, Soluplus® (polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol–graft copolymer) was selected as a solubilizer as well as film former for preparing ocular inserts and polyethylene glycol 400 (PEG-400) as a plasticizer. On the basis of an initial phase solubility study, the maximum concentration of Soluplus® possible was used for developing the inserts. An optimized formulation was obtained using a 32-factorial design. Two factors at three levels were used to design the ocular inserts. Soluplus® (X1) and the plasticizer, PEG-400 (X2), were set as the independent variables at various levels, and the Rel4h (drug release in 4 h, Y1) and tensile strength (Y2) were set as the dependent variables. A pre-formulation study was conducted to select suitable materials. Various physico-chemical parameters of the optimized formulation, including the tensile strength and folding endurance, were studied using FT-IR, DSC, XRD, and SEM. An in vitro dissolution study was conducted to determine the amount of drug released. There was no redness, swelling, or watering of the rabbit eye. It was concluded that the ocular inserts of the poorly soluble nepafenac developed using a graft-co-polymer enhanced the solubility and utilization of the drug for a prolonged period. [ABSTRACT FROM AUTHOR]

• Solubility of dexamethasone in the polymeric solution was increased by 5.2-fold. • The thermogel solution form a rigid gel at physiological temperature at eyes. • Dexamethasone was released in a sustained manner from the thermogel over 28 days. • Subconjunctivally injected DEX-thermogel could suppress the CNV development. Challenges of ophthalmic drug delivery arise not only from the limited solubility of hydrophobic therapeutics, but also the restricted permeability and fast clearance of drugs due to the complex anatomy and physiology of eyes. Excellent biocompatibility of a thermosensitive polymer, PLGA-PEG-PLGA (1800–1500–1800, LA:GA ratio = 3:1), as an ophthalmic delivery system was demonstrated in our previous work. In this study, delivery of dexamethasone using this thermogel via a single subconjunctival injection for prolonged treatment was evaluated with corneal neovascularization using an alkali-burn diseased model in rat. Solubility of dexamethasone in the polymeric solution was increased by 5.2-fold and the resulting drug-loaded solution formed in situ rigid gel at body temperature. Prolonged in vitro release of dexamethasone from the gel structure was noted. Dexamethasone gel formulation was demonstrated to be more effective in reducing the burn stimulus and neovascularization in the rat diseased model. The findings suggest the PLGA-PEG-PLGA in situ gelling system can be applied for ophthalmic drug delivery to achieve sustained drug release and improved efficacy. [ABSTRACT FROM AUTHOR]

The eye is a challenging organ for ophthalmic drug delivery due to the barriers associated with the anterior and posterior segments like nasolacrimal drainage, blinking, induced lacrimation, impermeability of corneal epithelial membrane, and blood-ocular barrier. Although there are conventional approaches, such as eye drop, ointment, suspension, implants, and injection, they suffer from limitations of low bioavailability, poor patient compliance (due to invasive approach and repeated dosing), and potential for several side effects. This review explored the various mucoadhesive polymers, derivatized polymers, and different modification methods for such polymer derivatization (via carboxymethylation, thiolation, and quaternization) for their effective drug delivery toward ophthalmic application. Various types of micro and nanoparticulate systems of such derivatized mucoadhesive polymer-based carriers have been also exemplified and discussed here for their improved medicinal efficacy. To address the issues associated with conventional ophthalmic formulations, mucoadhesive drug delivery has been proposed. The emerging technologies play an important role in the development of more efficient mucoadhesive carriers obtained by derivatization or modification of core polymers with various functional groups such as carboxymethyl, amine, and new generation thiols. Mucoadhesive polymers form bonding with mucin (hydrogen, covalent, electrostatic bonding, etc.) and enhance corneal residence time and cellular uptake of the drug. Mucoadhesive carriers are designed to associate with the micro and nanoparticulate systems to overcome the ocular barriers with improved therapeutic efficacy. [ABSTRACT FROM AUTHOR]

To improve ocular bioavailability of baicalein (BAI), trimethyl chitosan coated lipid nanoparticles of baicalein (TMC-BAI-LNPs) were prepared, optimized and characterized. The properties of TMC-BAI-LNPs such as morphology, particle size, zeta potential and fourier transform infrared spectroscopy were investigated. Additionally, molecular dynamics simulation was applied as a new method to evaluate drug-biological membrane interactions. Transmission electron microscopy showed that the LNPs were approximately spherical in shape with a smooth surface. TMC-BAI-LNPs had a particle size of 162.8 nm, a positive surface charge with a zeta potential of 26.6 mV. The entrapment efficiency and drug loading values of BAI in the formulation were 90.65% and 2.04%, respectively. Moreover, in vitro drug release revealed that TMC-BAI-LNPs had a sustained release effect. In vivo studies indicated TMC-BAI-LNPs had no ocular irritation and the AUC of TMC-BAI-LNPs was 3.17-fold than that of the control (p < 0.01). Molecular dynamics simulation data showed that BAI had a poor membrane permeability, which limited the ocular bioavailability. The results indicated that TMC-BAI-LNPs might open up a new avenue for ocular administration. Furthermore, molecular dynamics simulation could predict permeability of drugs. Unlabelled Image • TMC coated lipid nanoparticles of baicalein (TMC-BAI-LNPs) were prepared. • MD simulation was used as a novel method to evaluate TMC-BAI-LNPs. • TMC has been approved for biocompatibility and used as ophthalmic delivery system. • MD simulation showed BAI had a poor membrane permeability, which limited the ocular bioavailability. • TMC-BAI-LNPs have a great potential for ocular administration. [ABSTRACT FROM AUTHOR]

The aim of the present research work was to prepare and evaluate in situ gel forming ophthalmic drug delivery system loaded with brimonidine tartarate (BT). In this work, carbopol and hydroxy propyl methyl cellulose (HPMC), ophthalmic gel-forming mucoadhesive polymers, which gets converted to gel in the lachrymal fluid were used as in the preparation of pH t riggered in situ gel formulation. The formulations were then autoclaved at 121°C for 15 min and evaluated for pH, clarity, gelling capacity, drug content, viscosity, and in vitro release. The developed formulations exhibited extended release of drug over a period of 8 hours in in vitro studies and therefore it could increase the residence time in eye. The optimized formulations were finally tested for its ability to cause irritation in male albino rabbits. The results indicated that the formulations did not irritate or damage the cornea, iris and conjunctiva. [ABSTRACT FROM AUTHOR]

Eye drop solutions are widely used by the ophthalmologist to treat the anterior segment eye diseases. However, eye drop solutions have many limitations including low bioavailability, high dose requirements, and poor patient compliance. Contact lenses are used to deliver the ocular drugs with high ocular bioavailability due to its immediate location to cornea. To attend controlled and prolonged drug release from the contact lenses, scientists are working on various systems including polymeric nanoparticles, molecular imprinting, microemulsion, micelles, liposomes, implantation, supercritical fluids, and use of vitamin E. However, the changes in the critical lens properties like swelling, optical transparency, ion permeability, tensile strength, oxygen permeability, high burst release, issues during monomer extraction, sterilization and storage are yet to address. The review is focused on the commercial challenges with different methodologies to develop therapeutic contact lenses for commercial market. Many animal and clinical studies are under pipeline and it is likely that the therapeutic contact lenses will be commercialized in next few years. [ABSTRACT FROM AUTHOR]

The spread of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) outbreak beginning in March 2020. Currently, there is a lack of suitable dose formulations that interrupt novel coronavirus transmission via corneal and conjunctival routes. In the present study, we developed and evaluated a thermosensitive gelling system based on a selenium-containing polymer for topical ocular continuous drug release. In detail, di-(1-hydroxylundecyl) selenide (DHSe), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) were polymerized to form poly(DHSe/PEG/PPG urethane). The polymer was used to carry poorly water-soluble remdesivir (RDV) at room temperature to form the final thermosensitive in situ gel, which exhibited a typical sol-gel transition at 35 °C. The formed polymer was further characterized by rheology, thermology, and scanning electron microscopy. In vitro release studies and in vivo retention and penetration tests indicated that the thermogel provided the prolonged release of RDV. The RDV-loaded in situ gel was proven to be non-biotoxic against human corneal epithelial cells, with good ocular tolerance and biocompatibility in rabbit eyes.

Therapeutic ophthalmic contact lenses with prolonged drug release and improved bioavailability have been developed to circumvent tedious eye drop instillation. In this work, zwitterionic nanogels based on poly(sulfobetaine methacrylate) (PSBMA) were easily fabricated by one-step reflux-precipitation polymerization, with the advantages of being surfactant-free and morphology controlled. Then, the ophthalmic drug levofloxacin (LEV) was encapsulated into the nanogels. A set of contact lenses with varied nanogel-loading content was fabricated by the cast molding method, with the drug-loaded nanogels dispersed in pre-monomer solutions composed of 2-hydroxyethyl methacrylate (HEMA) and N-vinyl-2-pyrrolidone (NVP). The structure, surface morphology, water contact angle (WCA), equilibrium water content (EWC), transmittance, and mechanical properties of the contact lenses were subsequently investigated, and in vitro drug release and biocompatibility were further evaluated. As a result, the optimized contact lens with nanogel-loading content of 8 wt% could sustainably deliver LEV for ten days, with critical lens properties within the range of recommended values for commercial contact lenses. Moreover, cell viability assays revealed that the prepared contact lenses were cytocompatible, suggesting their significant potential as an alternative to traditional eye drops or ointment formulations for long-term oculopathy treatment.

Subvisible particles are a critical quality attribute of pharmaceutical products. The reliability of particle quantitation increases with the number of particles in the analyzed sample volume. However, for analyses of low-volume drug products, such as ophthalmic products for intravitreal injection or biopharmaceuticals in general, sample volumes as small as possible should be used to avoid pooling and consequently, the contamination with foreign particles. The aim of our study was to evaluate the variability of particle concentrations obtained by light obscuration measurements to define the minimum required analyzed sample volume to achieve statistically meaningful results by using conditions that are practically feasible. Statistical evaluation suggests that for particle concentrations close to a predefined limit, large sample volumes (a multiple of typical intravitreal product volumes) would be required for a high probability to correctly classify samples with respect to the predefined limit. Below a minimum analyzed volume, even a measurement result of 0 particles does not allow to conclude compliance with the respective particle concentration limit with sufficient certainty. A small analyzed volume could be justified as long as the measurement uncertainty remains acceptable compared with the predefined limit. [ABSTRACT FROM AUTHOR]

Owing to the discovery of a less soluble crystalline form (form 2) of cyclosporine (CsA), risks in solubility and physical stability of these formulations need to be revisited. This work focused on understanding the solubility behavior of various CsA forms in different media, including water, castor oil, and selected cosolvent micellar systems. In water, form 2 was approximately 8-9 times less soluble than form 1 (aka. tetragonal dihydrate). In neat nonaqueous solvent, for example, castor oil, form 3 (aka. orthorhombic hydrate) was found to have the lowest solubility and therefore the most stable form. In addition, the solubility-temperature relationship of CsA is complex and solvent-dependent. In aqueous vehicles, retrograde temperature dependence of solubility was observed in aqueous vehicles, that is, the solubility of CsA decreased with temperature, which was attributed to the effect of temperature on the strength of hydrogen bonding interactions; conversely, the solubility of CsA increased with temperature in nonaqueous solvents. In addition, the solubility of these CsA forms was very sensitive to temperature. Temperature-dependent form transformation was also observed in the media studied, with faster form conversion occurring at elevated temperatures. These studies provided key information to support the risk assessment for topical ophthalmic formulation development of CsA. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the present study was to improve the ocular delivery for ketorolac tromethamine (KT) used to treat inflammation of the eye. Methods: Eudragit nanoparticles loaded with KT were prepared and incorporated in polyvinyl alcohol (PVA) and hydroxyethyl cellulose (HEC) films. Nanoparticles were characterized by Fourier transform-infrared (FT-IR), scanning electron microscopy (SEM). Physicochemical properties and encapsulation effciency were investigated for nanoparticles. Also, the inserts were evaluated for their physiochemical parameters like percentage moisture absorption, percentage moisture loss, thickness and folding endurance. Results: Mean particle size and zeta potential were in range of 153.8-217 nm and (-10.8) - (-40.7) mV, respectively. The results show that the use of a surfactant has not led to any major change on drug loading. The loading increases with the amount of polymer. The insert had a thickness varying from 0.072 ± 0.0098 to 0.0865 ± 0.0035 mm. The thicknesses of the inserts and the folding endurance increased with the total polymer concentration. The physicochemical properties showed that the Eudragit® L-100 nanoparticles loaded PVA-HEC films could be an effective carrier for KT. Conclusion: For the first time, inserts of Eudragit nanoparticles were successfully prepared for ophthalmic drug delivery system to prevent frequent drug administration and enhance patient compliance. [ABSTRACT FROM AUTHOR]

Extending the delivery of drugs into the eyes while reducing systemic bioavailability is of utmost importance in the management of chronic ocular diseases. Topical application onto the lower eyelid skin, as an alternative to eye drops, is seen to be a valuable strategy in the treatment of chronic eye diseases. To elucidate the critical value of delivering drugs in solution onto the eyeball through the eyelid skin, pharmacokinetic studies of pilocarpine were conducted, and the results were verified using a direct pharmacodynamic study in rats. The mean residence time of pilocarpine after topical eyelid application to the eyelid skin, conjunctiva, eyeball, and plasma were 14.9, 8.50, 6.29, and 8.11 h, respectively. Conjunctiva and eyeball concentrations of pilocarpine at 8 h were 80-fold and 8-fold higher after topical eyelid application, respectively, than those for eye drops. Pupillary constriction was sustained over 8 h after topical eyelid application. Topical eyelid skin application exhibited a localized drug absorption and specific drug accumulation in the ocular tissues. Hence, it is rational to prepare topical formulations directed onto the eyelid skin, which is suitable for drugs required for long-term treatment. [ABSTRACT FROM AUTHOR]

The study was designed to fabricate the moxifloxacin nanostructured lipid carriers (MOX-NLCs) loaded in situ gel for opthalmic application to improve the corneal permeation and retention and also subside the toxic effect associated with intracameral injection of moxifloxacin in endophthalmitis treatment. Initially, Box-Behnken design was used to optimize the various factors significantly affecting the final formulation attributes. MOX-NLCs with particle size 232.1 ± 9.2 nm, polydispersity index 0.247 ± 0.031, zeta potential −16.3 ± 1.6 mV, entrapment efficiency 63.1 ± 2.4%, and spherical shape was achieved. The optimized MOX-NLCs demonstrated the Higuchi release kinetics with highest regression coefficient. Besides this, FTIR, differential scanning calorimetry, and X-ray diffraction results suggested that MOX had excellent compatibility with excipients. Furthermore, the results of ex-vivo permeation study demonstrated 2-fold higher permeation (208.7 ± 17.6 μg), retention (37.26 ± 2.83 μg), and flux (9.57 ± 0.73 μg/cm2 h) compared with free MOX in situ gel. In addition, MOX-NLCs exhibited normal corneal hydration and did not show any sign of structural damage to the corneal tissue as confirmed by histology. Therefore, the findings strongly suggest that MOX-NLCs in situ gel with higher permeation and retention can be a better alternative strategy to prevent and treat the endophthalmitis infection. [ABSTRACT FROM AUTHOR]

The eye is a very important, yet sensitive organ, presenting complex anatomy. To overcome its protective mechanisms, with the aim of improving drug delivery, drug encapsulation in nanocarriers is considered in this review. Chitosan is found to be an excellent drug carrier and its application in ophthalmology is being extensively researched. This mucoadhesive biopolymer can protect the encapsulated molecule, optimize its mode of action and minimize any existent risk. Moreover, chitosan and its derivatives may provide advantageous properties to the system such as thermoresponsivity and pH dependency. Finally, dual systems of chitosan with other carriers, such as poly (lactic-co-glycolic acid) and alginate, are also mentioned in this review, as they may offer additional benefits such as higher permeation due to different interaction of each carrier with the corneal layers. [ABSTRACT FROM AUTHOR]

Purpose: To examine if current development on using contact lenses for drug delivery of cysteamine to treat ocular symptoms of cystinosis can be tinted to mitigate photophobia common in patients by reducing transmittance Methods: Commercial contact lenses were placed in a carbon black solution to examine loading after lens synthesis. Silicone hydrogel contact lenses were also synthesized with carbon black added prior to UV curing. Transmittance was measured using UV–vis spectrophotometry over the range of 190–1190 nm and compared to unmodified contact lenses. Lens parameters of refractive index, ion permeability, and Young's modulus were measured using a refractometer, release of sodium chloride, and the cantilever method. Cysteamine release was measured by loading lenses into 5% cysteamine solution and then monitoring the release of the drug using UV–vis spectrophotometry. Vitamin E diffusion barriers were also added to lenses via ethanol solution, and the release of cysteamine from these modified lenses was also examined. Results: No leeching of carbon black was detected during experiments. Loading of pre-made contact lenses led to uneven distribution of carbon black throughout lens. Adding 0.3% carbon black to lens monomer solution prior to UV-curing led to even distribution and a transmittance reduction of approximately 50%. Ion permeability was reduced from 6.19 ± 0.90 x 10−3 to 1.28 ± 0.06 x 10−3 mm2 min−1, and Young's modulus was decreased from 1.58 ± 0.08 to 1.29 ± 0.06 MPa. Cysteamine releases from carbon black lenses with and without vitamin E were comparable to controls, although the loading solution of vitamin E/ethanol had to be tripled to achieve a similar mass loading to control. Conclusions: Carbon black increases the softness of contact lenses, but a loading of 0.3% maintains lens parameters required for wear. The release of cysteamine is also possible with carbon black lenses, albeit requiring a higher loading concentration of vitamin E to achieve similar release times. [ABSTRACT FROM AUTHOR]

Graphical abstract Axitinib was loaded into self-assembled micelles by for ocular surface treatment of corneal neovascularization. Abstract The development of new blood vessels is directly related to the occurrence of eye diseases. Anti-angiogenic drugs can theoretically be extended to the treatment of ophthalmic diseases. In this study, axitinib, a class of tyrosine kinase inhibitors, was loaded via the amphiphilic copolymer MPEG-PCL, improving its dispersibility in water. Axitinib-loaded micelles showed low toxicity in concentration gradient assays. Additionally, multiple doses by scratch assay confirmed that axitinib had no significant effect on normal cell migration, and biosafety test results showed good cell compatibility. After we established the corneal neovascularization model after an alkali burn in rats, the anti-angiogenic efficacy was tested, with dexamethasone as a positive control. The results showed that axitinib-loaded micelles had anti-angiogenic effects without obvious tissue toxicity. As a class of targeted tyrosine kinase inhibitors, axitinib can be used in the treatment of ocular neovascular diseases through nanocrystallization. [ABSTRACT FROM AUTHOR]

Abstract This article reports on electrohydrodynamic atomization to engineer on-demand novel coatings for ocular contact lenses. A formulation approach was adopted to modulate the release of timolol maleate (TM) using chitosan and borneol. Polymers polyvinylpyrrolidone and poly (N-isopropylacrylamide) were utilized to encapsulate TM and were electrically atomized to produce optimized, stationary contact lens coatings. The particle and fiber diameter, thermal stability, material compatibility of the formed coatings, their in vitro release-modulating effect, and ocular tolerability were investigated. Results demonstrated highly stable nanomatrices with advantageous morphology and size. All formulations yielded coatings with high TM encapsulation (>88%) and excellent ocular biocompatibility. Coatings yielded biphasic and triphasic release, depending on composition. Kinetic modeling revealed a noticeable effect of chitosan; the higher the concentration, the more the release of TM because of chitosan swelling, with the mechanism changing from Fickian diffusion (1% w/v; n = 0.5) to non-Fickian (5% w/v, 0.45 < n < 0.89). The use of electrohydrodynamic atomization has not yet been explored in depth within the ocular research remit, engineering on-demand lens coatings capable of sustaining TM release. This is likely to offer an alternative dosage form for management of glaucoma with particular emphasis on improving poor patient compliance. [ABSTRACT FROM AUTHOR]

Abstract Triblock poloxamer copolymer (PM) has been extensively utilized to deliver various ophthalmic pharmaceutical compounds. The aim of efficient ophthalmic drug delivery strategy is to attain the longer precorneal resident time and good bioavailability of drugs. In this pursuit, the influence of cellulose nanocrystals (CNC) on the in situ gelation behavior of PM and in vitro release of pilocarpine hydrochloride from the nanocomposites formulations was studied. The critical concentration of gelation of PM being 18% (wt/v) was dropped to 16.6% (wt/v) by the addition of a very low percentage of CNC. The reinforcing nature of CNC via H-bonding in the in situ nanocomposite gel also led to an increase in gel strength along with the sustained release of loaded drugs when compared with the pure PM gel. All formulations revealed that the drug release mechanism is controlled by the Fickian diffusion. Thus, the CNC has a significant effect on the gelation behavior, gel strength, and drug release kinetics of PM-CNC formulations. Graphical abstract Unlabelled Image Highlights • Reduced critical concentration of thermo-responsive gelation of poloxamer gel. • Cellulose nanocrystals influenced the in situ gelation behavior of poloxamer gel. • Increased poloxamer gel strength via H-bonds in the in situ nanocomposite gel. • Sustained release of loaded drugs from the nanocomposite gel. • Non-cytotoxic ODDS with reduced dissolution properties. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract In this paper, we presented a simple yet versatile strategy to generate a high drug payload nanoparticles by the combination with small molecular assembly and polymeric assembly for topical suppression of ocular inflammation. Upon physical mixing of the succinated triamcinolone acetonide (TA-SA) supramolecular hydrogel with the poly (ethylene glycol)-poly (ɛ-caprolactone)-poly (ethylene glycol) (PECE) aqueous solution at 37 °C, TA-SA/PECE nanoparticles formed spontaneously and characterized thoroughly by transmission electron microscopy (TEM), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The formed TA-SA/PECE nanoparticles displayed a comparable in vitro anti-inflammatory efficacy to that of native triamcinolone acetonide (TA), through a significant downregulation of various proinflammatory cytokines levels (e.g., NO, TNF-α) in a lipopolysaccharide (LPS) actived RAW264.7 macrophage. Meanwhile, the enhanced transcorneal drug permeability of TA-SA/PECE nanoparticles over that of TA suspension was clearly observed in an isolated rabbit cornea. Intraocular biocompatibility test demonstrated that TA-SA/PECE nanoparticles presented good biocompatibility after topical instillation during entire study period. More importantly, the TA-SA/PECE nanoparticles displayed superior therapeutic efficacy over that of the TA suspension in the endotoxin-induced uveitis (EIU) rabbit model via decreasing neutrophil infiltration in anterior chamber. Overall, the proposed TA-SA/PECE nanoparticles might be a promising candidate for uveitis therapy. [ABSTRACT FROM AUTHOR]

A hollow cylinder intravitreal implant was developed to achieve sustained release of protein to the retina for the treatment of retinal diseases. Hollow cylinders were fabricated by molding and cross-linking hyaluronic acid, the major component of the vitreous humor. Hollow cylinders were filled with a concentrated protein solution, and the properties of the cylinder walls were tested. Cross-linked hyaluronic acid hydrogels with swelling degrees as low as 2.7 were achieved as a means to extend the release of protein. Hollow cylinders were capable of releasing an antigen-binding fragment for over 4 months at a maximum release rate of 4 μg per day. Protein release from hollow cylinders was modeled using COMSOL Multiphysics ® software, and diffusion coefficients between 1.0 × 10 −11 and 3.0 × 10 −11 cm 2 /s yielded therapeutically effective levels of protein. Cylinders with a 1 mm outer radius were capable of loading >1 mg of protein while releasing at least 2.5 μg a day for over 4.5 months. Although smaller cylinders facilitate intravitreal placement, decreasing the cylinder radius severely limited drug loading. Design of hollow cylinder intravitreal implants must balance high drug loading to reduce device size with control of the diffusion coefficient to sustain protein release. [ABSTRACT FROM AUTHOR]

The present study aimed at formulating and optimizing natamycin (NT)-loaded polyethylene glycosylated nano-lipid carriers (NT-PEG-NLCs) using Box-Behnken design and investigating their potential in ocular applications. Response surface methodology computations and plots for optimization were performed using Design-Expert ® software to obtain optimum values for response variables based on the criteria of desirability. Optimized NT-PEG-NLCs had predicted values for the dependent variables which are not significantly different from the experimental values. NT-PEG-NLCs were characterized for their physicochemical parameters; NT's rate of permeation and flux across rabbit cornea was evaluated, in vitro , and ocular tissue distribution was assessed in rabbits, in vivo . NT-PEG-NLCs were found to have optimum particle size (<300 nm), narrow polydispersity index, and high NT entrapment and NT content. In vitro transcorneal permeability and flux of NT from NT-PEG-NLCs was significantly higher than that of Natacyn ® . NT-PEG-NLC (0.3%) showed improved delivery of NT across the intact cornea and provided concentrations statistically similar to the marketed suspension (5%) in inner ocular tissues, in vivo , indicating that it could be a potential alternative to the conventional suspension during the course of fungal keratitis therapy. [ABSTRACT FROM AUTHOR]

In situ forming ophthalmic gels need to be fine tuned considering all the biopharmaceutical challenges of the front of the eye in order to increase drug residence time at the application site resulting in its improved bioavailability and efficacy. The aim of this study was to develop in situ forming ophthalmic poloxamer P407/poloxamer P188/chitosan gel fine tuned in terms of polymer content, temperature of gelation, and viscosity. Minimizing the total polymer content while retaining the advantageous rheological properties has been achieved by means of D-optimal statistical design. The optimal in situ forming gel was selected based on minimal polymer content (P407, P188, and chitosan concentration of 14.2%, 1.7%, and 0.25% w/w, respectively), favorable rheological characteristics, and in vitro resistance to tear dilution. The optimal in situ forming gel was proved to be robust against entrapment of active pharmaceutical ingredients making it a suitable platform for ophthalmic delivery of active pharmaceutical ingredients with diverse physicochemical properties. [ABSTRACT FROM AUTHOR]

Econazole is a feasible alternative treatment in the management of fungal keratitis. Nevertheless, its low water solubility is considered the main limitation to the incorporation into ophthalmic formulations. In this work, econazole nitrate is solubilized by using cyclodextrins to achieve an optimum therapeutic concentration. Phase solubility diagrams suggest α-cyclodextrin as the most effective cyclodextrin and later the inclusion complex formed with this one was characterized in solution by 1D, 2D-NMR, and molecular modeling. Econazole-α-cyclodextrin inclusion complex was included in 2 types of ocular hydrogels: a natural polysaccharides ion-sensitive hydrogel and a hyaluronic acid hydrogel. Both of them show no ocular irritation in the hen's egg test on chorioallantoic membrane assay and a controlled econazole release over time. Permeability studies suggest that hydrogels do not modify the econazole nitrate permeability through bovine cornea in comparison with an econazole-α-cyclodextrin inclusion complex solution. Finally, ocular biopermanence studies performed using positron emission tomography show these hydrogels present a high retention time on the eye. Results suggest the developed formulations have a high potential as vehicles for the econazole topical ocular administration as fungal keratitis treatment. [ABSTRACT FROM AUTHOR]

The low bioavailability exhibits by conventional ocular formulation owing to rapid precorneal clearance and lower corneal permeability can be overcame by the application of the gelling system. In the present study, a prodrug supramolecular hydrogel derived from succinated dexamethasone (Dex-SA) was fabricated using a pH hydrolytic strategy and explored as a “self-delivery” system for ophthalmic drugs. The self-assembled Dex-SA supramolecular hydrogel exhibited a typical nano-fibrous microstructure and was thixotropic. Both dexamethasone (Dex) and Dex-SA prodrug sustainably released from Dex-SA supramolecular hydrogel in a period of 120 h in vitro release study, and the initial pH value of hydrogel significantly influence on the release ratio of Dex/Dex-SA. Furthermore, the lyophilized Dex-SA supramolecular hydrogel displayed long-term stability without causing any apparent hydrolysis of Dex-SA at −20 °C over 30 day and quickly re-formed a hydrogel after dissolving into aqueous solution. The formed Dex-SA supramolecular hydrogel had lower cytotoxicity than Dex at drug concentration up to 2.5 mM, and exhibited a comparable anti-inflammatory efficacy to a Dex sodium phosphate (Dexp) aqueous solution in lipopolysaccharide-activated RAW264.7 macrophages. Topical instillation of the Dex-SA supramolecular hydrogel showed excellent intraocular biocompatibility and it was not an irritant in rabbit eyes. More importantly, the Dex-SA supramolecular hydrogel provided a prolonged precorneal retention and significantly enhanced the ocular bioavailability over Dexp aqueous solution after topical instillation. Overall, this work illustrates an effective approach for the development of prodrug supramolecular hydrogels to extend the precorneal retention and enhance ocular bioavailability of drugs after topical instillation. [ABSTRACT FROM AUTHOR]

Conventional eyedrops commonly used to deliver ophthalmologic treatments do not provide a sustained delivery of the drug, since a large portion of the intended dose is lost through eye drainage immediately following application. Micrometric sized crosslink gel based on copolymers incorporating thermal-sensitive copolymers were proposed for use in ophthalmic drug delivery. Eyedrops based on a thermoresponsive polymer were developed by mixing poly(acrylic acid- graft - N -isopropylacrylamide) (PAAc- graft -PNIPAAm) with PAAc- co -PNIPAAm gel and incorporating [ 3 H]-epinephrine for in vitro evaluation of ophthalmic drug release. Polymeric eyedrops are clear solutions at room temperature but undergo partial solidification to a soft thin film on coming into contact with the corneal surface. On evaluation of the in vitro release kinetics of the embedded [ 3 H]-epinephrine, PAAc- graft -PNIPAAm was found to exhibit faster drug release, while the mixture of PAAc- graft -PNIPAAm and PAAc- co -PNIPAAm gel showed a more sustained release profile and identifying the anomalous transport mechanism as a key factor. Intraocular pressure (IOP) was monitored by administration of epinephrine in polymeric eyedrops effectively reduced IOP for 36 h, which is a considerable prolongation of the effect compared to the 8-h IOP decrease observed following administration via traditional eyedrops. Overall, our results indicate that the kinetics of drug release from the polymeric eyedrops are determined by crosslinking density, which affects the formation of capillary networks in the polymer matrix and thereby regulates drug diffusion into the polymeric network, hence considered as feasible approach to controlled drug release in ophthalmic drug delivery. [ABSTRACT FROM AUTHOR]

For the treatment and prevention of ocular diseases, most patients are treated with conventional drug delivery formulations such as eye drops or ointments. However, eye drops and ointments suffer from low patient compliance and low effective drug concentration at the target site. Therefore, new medical devices are being explored to improve drug delivery to the eye. Over the years, various delivery devices have been developed including resorbable devices, oval- and ring-shaped devices, rod-shaped devices, punctum plugs, contact lenses and corneal shields. Only a few devices (eg. Mydriasert ® , Ozurdex ® , Surodex ® , Iluvien ® , Lacrisert ® and Retisert ® ) have made it to the market while others are being investigated in clinical trials. Altogether, there is a need for enhanced topical drug delivery. Only by working together (academia, industry and authorities) and by exploring parallel strategies (new drug delivery devices, enhanced drug formulations, better understanding of the pharmacokinetic properties), the therapeutic effect of drug treatments can be improved. [ABSTRACT FROM AUTHOR]

Thiolated poly(aspartic acid) is known as a good mucoadhesive polymer in aqueous ophthalmic formulations. In this paper, cyclodextrin-modified thiolated poly(aspartic acid) was synthesized for the incorporation of prednisolone, a lipophilic ophthalmic drug, in an aqueous in situ gellable mucoadhesive solution. This polymer combines the advantages of cyclodextrins and thiolated polymers. The formation of the cyclodextrin-drug complex in the gels was analyzed by X-ray powder diffraction. The ocular applicability of the polymer was characterized by means of physicochemical, rheological and drug diffusion tests. It was established that the chemical bonding of the cyclodextrin molecule did not affect the complexation of prednisolone, while the polymer solution preserved its in situ gellable and good mucoadhesive characteristics. The chemical immobilization of cyclodextrin modified the diffusion profile of prednisolone and prolonged drug release was observed. The combination of free and immobilized cyclodextrins provided the best release profile because the free complex can diffuse rapidly, while the bonded complex ensures a prolonged action. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the in vivo efficacy of several timolol (TM)-loaded liposomal formulations with current TM antiglaucoma treatment (aqueous 0.5% w/v eye drops). In this study, conventional liposomes (CL) and deformable liposomes, without (DL1) and with ethanol (DL2) were prepared and characterized. In addition, in vitro release and permeation studies, as well as in vivo lowering intraocular pressure (IOP) and biocompatibility studies were performed. It was found that the quali and quantitative lipid bilayer composition played a significant role in modifying the physical properties of vesicles. The deformability study and electronic microscopy images revealed that membrane elasticity of DL1 and DL2 was much higher than CL. However, in vitro permeation results showed that the flux and permeability coefficient were significantly higher in CL compared to DL. The IOP study revealed that TM-loaded CL showed the best pharmacological activity, in comparison to deformable vesicles. Compared to the eye drops, CL formulation could equally reduce the IOP but using a concentration 10-fold lower, whereas the effective time was significantly longer. In addition, the formulations showed no irritant effects after instillation on the ocular surface. [ABSTRACT FROM AUTHOR]

Background: Strabismus adversely affects psychosocial and functional aspects; while its correction impacts positively. Aim: The aim was to evaluate the gains in scores: Overall scores (OASs), psychosocial subscale scores (PSSs) and functional subscale scores (FSSs) following successful surgical alignment. Settings and Design: We evaluated changed scores in the adult strabismus 20 (AS-20) questionnaire, administered before and after successful surgery. Materials and Methods: Thirty adults horizontal strabismics, were administered the AS-20, at baseline, and at 6-week and 3-month. Group-wise analysis was carried out based on gender, strabismus type (esotropia [ET] or exotropia [XT]), back-ground and amblyopia. Statistical Analysis: We used Wilcoxon, and Mann-Whitney U-tests. Significance was set at P ≤ 0.05. Results: At baseline, there were no significant differences within the groups, except that those with amblyopia significantly scored less than nonamblyopes in OAS (median scores: 53.8 vs. 71.3; P = 0.009) and FSS (56.3 vs. 85.3; P = 0.009). OAS, PSS and FSS showed significant gains at 6-week and 3-month (all Wilcoxon P < 0.001). Compared with males, females showed significantly more gain at 3-month (OAS: 37.9 vs. 28.7; P = 0.02), on account of PSS gain (49.6 vs. 37.5; P = 0.01). The ET performed better than XT only on the FSS at 6-week (28.7 vs. 15.0; P = 0.02). Vis-à-vis the nonamblyopes, the amblyopes showed significantly more benefit at 6-week alone (OAS: 18.7 vs. 28.7; P = 0.04), largely due to gains in PSS. Conclusions: Successful strabismus surgery has demonstrated significant gains in psychosocial, functional and overall functions. There is some evidence that gains may be more in females; with a trend to better outcomes in ET and amblyopes up to 6-week.

Purpose: To report visual and anatomic outcomes of chronic macular hole surgery, with analysis of pre-operative OCT-based hole size and post-operative closure type. Settings and Design: An IRB-approved, retrospective case series of 26 eyes of 24 patients who underwent surgery for stage 3 or 4 idiopathic chronic macular holes at a tertiary care referral center. Statistical Analysis: Student′s t-test. Results: Nineteen of 26 eyes (73%) had visual improvement after surgery on most recent exam. Twenty-one of 26 eyes (81%) achieved anatomic closure; 16 of 26 eyes (62%) achieved type 1, and five of 26 eyes (19%) achieved type 2 closure. Post-operative LogMAR VA for type 1 closure holes (0.49) was significantly greater than for type 2 closure and open holes (1.26, P < 0.003 and 1.10, P < 0.005, respectively), despite similar pre-operative VA (P = 0.51 and 0.68, respectively). Mean pre-operative hole diameter for eyes with type 1 closure, type 2 closure, and holes that remained open were 554, 929, and 1205 microns, respectively. Mean pre-operative hole diameter was significantly larger in eyes that remained open as compared to eyes with type 1 closure (P = 0.015). Conclusion: Vitrectomy to repair chronic macular holes can improve vision and achieve long-term closure. Holes of greater than 3.4 years duration were associated with a greater incidence of remaining open and type 2 closure. Larger holes (mean diameter of 1205 microns) were more likely to remain open after repair.

Aim: We sought to identify differences in the following measures of the ocular response analyser (ORA) between primary open angle glaucoma (POAG) and exfoliative glaucoma (EXG) patients: Corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated intraocular pressure (IOPcc) and Goldmann-correlated intraocular pressure (IOPg). We also sought to relate these ORA measures with central corneal thickness (CCT). Materials and Methods: This cross-sectional study was conducted on a total of 162 individuals (46 EXG patients, 66 POAG patients and 50 healthy subjects without any ocular and systemic disease). ORA measurements were performed, and a minimum of three readings were obtained from each test subject. Groups were compared according to their ORA parameters. Results: The mean CH levels of the EXG, POAG and healthy subjects were 7.6 ± 2.1, 9.1 ± 1.9 and 9.6 ± 1.7 mmHg, respectively. CH was significantly lower in the EXG patients compared to the other groups (P < 0.001).The mean CRF levels of the EXG, POAG and healthy subjects were 9.0 ± 2.0, 10.1 ± 1.7 and 9.8 ± 1.8mmHg, respectively. CRF levels in the eyes of the EXG patients were significantly lower compared to those of either the POAG patients (P = 0.005) or the healthy subjects (P = 0.03), but there was no significant difference in CRF levels between the POAG patients and the healthy subjects (P = 0.59). There was a significant positive correlation between CH and CCT in the EXG patients and healthy subjects (P < 0.001), but this correlation was not present in the POAG patients (P = 0.70). Conclusions: In this study, CH and CRF were found to be significantly reduced in the eyes of EXG patients compared to both the POAG patients and healthy subjects. Reduced CH in EXG patients might result in decreased support of peripapillary scleral structure and increased damage to the optic nerve during IOP increase.

Purpose: Our purpose was to study the clinical manifestation and course of optic pit maculopathy using Spectral Domain Optical Coherence Tomography (SD- OCT) images. Materials and Methods: We used SD-OCT to examine 20 eyes of 19 patients with a macular detachment in combination with an optic. Results: We observed five different fovea appearances in regard to fluid localization. In five eyes, we recorded changes in the fluid distribution with SD-OCT. In 17/20 eyes, we noted a communication between the perineural and subretinal and/or intraretinal space at the margin of the optic disc. Conclusion: 3-dimensional SD-OCT (3D-SDOCT) scans revealed a three-fold connection, between subretinal and intraretinal space, perineural space, and the vitreous cavity. Therefore, we suppose that intraretinal or subretinal fluid in optic pit maculopathy may have both a vitreous and cerebrospinal origin. A membrane, covering the optic nerve was noted in 14 cases. Even if it seems intact in some B-scans, it is not complete in others several micrometers apart. Additionally, we observed fluid accumulation below the margin of the optic disc and hyperreflective porous tissue in the optic disc excavation. Those findings do not influence the course of maculopathy.

The topically applied drugs as drops are washed off from the eye in very short period, resulting in low ocular bioavailability of drugs. Number of approaches have been attempted to increase the bioavailability and the duration of action of ocular drugs. This review provides an insight into various novel approaches; hydrophilic nanogels, solid lipid nanoparticles, and nanosponges applied very recently in the delivery of insoluble drugs, prolonging the ocular residence time, minimize pre-corneal drug loss and, therefore, bioavailability and therapeutic efficacy of the drugs. Despite various scientific approaches, efficient ocular drug delivery remains a challenge for pharmaceutical scientists.

Purpose: To ascertain the effect of digitally induced large angle strabismus and its correction on social bias against strabismic adults. Subjects and Methods: This prospective, observational study included 10 orthotropic subjects whose face photographs were digitally altered to produce esotropia, exotropia, and hypertropia. Three batches of non-medical professionals, each consisting of 14 subjects, adjudged personality traits of the altered face photographs on a 10-item questionnaire. The same evaluators effected the appraisal of the orthotropic photographs. The personality score of the strabismic photograph of a subject was compared with its own orthotropic photograph. Results: The 10 subjects whose photographs were digitally modified were of the same age (21 years) and had equal gender distribution. The evaluation of the photographs was performed by 42 evaluators aged 38.3 ± 14.9 years, of whom 21 were males. Different personality traits were rated negatively in the strabismic photographs. The statistically significant negative impact was apparent on more number of personality traits for esotropia (7 out of 10) as compared to exotropia (4 out of 10) or hypertropia (3 out of 10). Rating of the strabismic photographs was significantly lower by female evaluators (P = 0.006). However, there was no difference whether the subject evaluating the photograph of the strabismic individual was of the same gender or the opposite gender. Internal consistency of the questionnaire was excellent (Cronbach′s Alpha = 0.81). Conclusion: There was a significant negative impact of strabismus on the perceived personality traits of the digitally altered face photographs of the adults when compared to their orthotropic photograph.

Background and Aims: This study documents a survey of final-year ophthalmology postgraduate students on the subject of their residency training. A similar survey conducted 7 years ago published in IJO had concluded that the residency program was not up to expectations in many centers. Our study aimed to see if ophthalmology training and student perceptions differed since then. Materials and Methods: For our study, we added a few questions to the same questionnaire used in the article "which is the best method to learn ophthalmology? Resident doctors′ perspective of ophthalmology training" published in IJO, Vol. 56 (5). Results: Forty-nine students (62.02%) returned completed forms. Most students desired an orientation program on entering residency, and wished to undergo diagnostic training initially. Case-presentation with demonstration and Wet-lab learning were most preferred. There was a big difference between the number of surgeries students actually performed and the number they felt would have been ideal. Conclusion: On the whole, the students still felt the need for improved training across all aspects of ophthalmology.

Purpose: To study the relationship between the axial length and personal A-constant for the 1-piece Tecnis (Abbott ZCB00), AcrySof MA60AC (Alcon) and the Quatrix aspheric preloaded (CROMA) intraocular lenses (IOL). Materials and Methods: Patients matching the inclusion criteria were further subdivided according to the implanted IOL in this prospective comparative study. The obtained refractive outcomes were introduced into the formula installed in the biometry machine (Humphrey model 820 ultrasonic biometer) to obtain the personal A-constant for each eye. Polynomial regression analysis was done to study the individualized A-constant for each type of IOL in relation to preoperative axial length measurement. Results: Two hundred and forty five eyes of 186 patients were enrolled into this study, of whom 73 eyes with Tecnis 1-piece, 116 eyes with MA60AC, and 56 eyes with Quatrix. The median of personalized A-constant for Tecnis 1-piece, MA60AC, and Quatrix were 119.21 (SD 1.3, Std. Mean error 0.15), 119 (SD 1.2, Std. Mean error 0.11) and 120.4 (SD 1.2, Std. Mean error 0.16) respectively. Regression plots for the same range of axial length among all the groups showed that the Tecnis1 group followed the same pattern of the Quatrix group in which there was a linear relationship of a trend towards myopia when the axial length had increased and a hyperopic shift when decreased. This relationship changed into a plateau when the axial length became in the range of 23.5 mm to 27 mm in the MA60AC group. Conclusions: Personal A-constant follows different trends with different IOLs even for the same range of axial length.