Infectious Ophthalmic Diseases

Infectious ophthalmic disease is a spectrum of eye diseases caused by a variety of pathogens. These infectious agents can target various structures of the eye, from the external surface to the internal structures, leading to a spectrum of sight-threatening complications. Protheragen is at the forefront of developing innovative drug and therapy solutions for hereditary ophthalmic diseases.

Introduction to Infectious Ophthalmic Diseases

Infectious ophthalmic disease drug and therapy development refers to the preclinical research and translational pipeline focused on creating targeted interventions to prevent, treat, or eradicate ocular infections caused by pathogenic microorganisms. These infections, driven by bacteria, viruses, fungi, parasites, or prions, can affect any ocular tissue—including the cornea, conjunctiva, uvea, retina, and orbital structures—and may lead to vision impairment or blindness if left untreated. Preclinical development in this field prioritizes unraveling host-pathogen interactions in ocular microenvironments, validating antimicrobial targets, and evaluating candidate therapies for efficacy, safety, and ocular bioavailability before advancing to clinical trials.

The preclinical pathway for infectious ophthalmic therapies is distinguished by its focus on overcoming unique ocular barriers, including the blood-ocular barrier (BOB), corneal epithelium, and tear film, which limit drug penetration and efficacy. Core objectives include optimizing antimicrobial activity against target pathogens, minimizing off-target effects on delicate ocular tissues, and reducing the risk of antimicrobial resistance (AMR)—a growing global concern in ophthalmology. Preclinical studies integrate in vitro microbiological assays, ex vivo ocular tissue models, and in vivo infection models to generate data on therapeutic pharmacokinetics (PK), pharmacodynamics (PD), safety profiles, and mechanism of action, all critical for supporting Investigational New Drug (IND) applications.

Fig.1 Anatomy of the eye. (Lu L. J., et al., 2016)

This development process is tailored to the specific pathogen class and infection site. For example, topical therapies for corneal infections require formulations that enhance corneal permeation and prolonged residence time, while intraocular therapies targeting endophthalmitis must navigate the BOB to reach the vitreous humor. Preclinical validation also includes assessments of pathogen-specific virulence factors, such as bacterial biofilm formation in keratitis or viral latency in herpetic retinitis, as these factors directly influence therapeutic design and efficacy endpoints. Rigorous preclinical testing ensures that candidates address unmet medical needs, including multidrug-resistant (MDR) ocular infections and rare infectious conditions with limited treatment options.

Types of Infection in Ophthalmic Diseases

• Bacterial Ocular Infections
  Bacterial infections are a leading cause of acute ocular morbidity, with pathogens varying by tissue involvement. Corneal infections (keratitis) are commonly caused by Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, and Haemophilus influenzae, with MDR strains of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) posing significant therapeutic challenges. Preclinical models of bacterial keratitis often use rabbit or mouse corneas inoculated with clinical isolates, enabling evaluation of antimicrobial efficacy via corneal opacity scoring, bacterial load quantification, and histopathological analysis of inflammation. Endophthalmitis, an intraocular infection of the vitreous and aqueous humor, is frequently linked to Staphylococcus epidermidis (post-surgical) and Streptococcus viridans (endogenous), requiring preclinical models that mimic intraocular pathogen dissemination and host immune responses.
• Viral Ocular Infections
  Viral ocular infections are characterized by persistent or recurrent disease, driven by pathogens with tropism for ocular tissues. Herpes simplex virus type 1 (HSV-1) is the primary cause of herpetic keratitis, the leading infectious cause of corneal blindness worldwide, while varicella-zoster virus (VZV) can cause acute retinal necrosis (ARN) and herpes zoster ophthalmicus. Adenoviruses are responsible for epidemic keratoconjunctivitis, a highly contagious condition affecting the conjunctiva and cornea. Preclinical research relies on cell culture models (e.g., human corneal epithelial cells, retinal pigment epithelium [RPE] cells) and animal models (e.g., mouse HSV-1 keratitis models, rabbit adenovirus conjunctivitis models) to study viral replication, latency, and immune-mediated tissue damage, as well as to test antiviral therapies targeting viral DNA polymerase, glycoproteins, or host cell entry receptors.
• Fungal Ocular Infections
  Fungal ocular infections are often opportunistic, affecting immunocompromised individuals or those with ocular trauma involving plant material. Keratitis caused by filamentous fungi (e.g., Fusarium spp., Aspergillus spp.) and yeast (e.g., Candida albicans) is associated with high morbidity due to delayed diagnosis and limited antifungal efficacy. Endophthalmitis from Candida spp. is a common complication of systemic candidiasis. Preclinical models for fungal infections include in vitro assays measuring minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) in ocular cell lines, as well as in vivo models using immunocompetent and immunocompromised mice or rabbits to assess antifungal activity, tissue penetration, and host inflammatory responses. These models are critical for evaluating novel antifungals, as existing agents (e.g., azoles, polyenes) often have poor ocular bioavailability or significant toxicity.
• Parasitic and Protozoal Ocular Infections
  Parasitic ocular infections are endemic in tropical and subtropical regions, with pathogens such as Toxoplasma gondii, Onchocerca volvulus, and Acanthamoeba spp. causing severe vision loss. Toxoplasma gondii leads to ocular toxoplasmosis, the most common cause of infectious posterior uveitis, while Acanthamoeba keratitis is a rare but devastating infection associated with contact lens use. Preclinical research uses in vitro culture systems (e.g., Acanthamoeba trophozoite and cyst models, Toxoplasma-infected RPE cells) and animal models (e.g., mouse ocular toxoplasmosis models, hamster Acanthamoeba keratitis models) to study parasite lifecycle, tissue tropism, and therapeutic targets. These models support the development of antiparasitic therapies that target parasite metabolism, cell division, or host-parasite interaction pathways.

Table 1. Examples of ocular infections causing sight loss. (Lu L. J., et al., 2016)

Disclaimer: Protheragen focuses on providing preclinical research service. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.

Our Services

The development of effective drugs and therapies for infectious ophthalmic diseases has been an ongoing challenge, but significant progress has been made in recent years. Protheragen, a leading biotechnology company with extensive expertise in ophthalmology, has been at the forefront of these advancements.

Pathogen Characterization and Target Validation

Protheragen provides comprehensive pathogen characterization services to support target validation for infectious ophthalmic therapies. This includes isolation and identification of clinical ocular pathogens (bacteria, viruses, fungi, parasites) from patient samples, as well as genomic sequencing and virulence factor analysis to identify pathogen-specific targets. We offer functional validation assays to assess the role of candidate targets in pathogen survival, replication, or tissue invasion, using in vitro models such as pathogen-infected ocular cell lines. Clients can access support for antimicrobial susceptibility testing (AST), including MIC, MFC, and minimum bactericidal concentration (MBC) assays, to identify susceptible and resistant pathogen strains and validate target-based therapies.

Custom Preclinical Infection Model Generation

We develop tailored in vitro, ex vivo, and in vivo infection models to recapitulate key features of infectious ophthalmic diseases. In vitro models include pathogen-infected ocular cell lines (corneal epithelial cells, RPE cells, conjunctival epithelial cells) and 3D organoid models (corneal organoids, retinal organoids) that mimic human ocular tissue architecture. Ex vivo models use freshly isolated ocular tissues (rabbit or porcine corneas, human donor eyes) to evaluate therapeutic penetration and efficacy in a physiological context. In vivo models encompass pathogen-specific animal models, such as rabbit bacterial keratitis models, mouse HSV-1 keratitis models, and immunocompromised mouse fungal endophthalmitis models, all subjected to rigorous phenotypic characterization, including clinical scoring, pathogen load quantification, and histopathological analysis.

Therapeutic Efficacy Evaluation

Our preclinical efficacy services assess the activity of candidate therapies against infectious ocular pathogens. For antimicrobial agents, we conduct in vitro efficacy assays, including broth microdilution, agar diffusion, and time-kill curves, to measure pathogen growth inhibition or eradication. In vivo efficacy studies evaluate therapeutic impact on disease progression via clinical endpoints (corneal opacity, conjunctival inflammation, vitreous haze), pathogen load reduction, and tissue damage mitigation. For antiviral and antiparasitic therapies, we assess viral/parasite replication inhibition, latency reversal, and host immune response modulation using molecular assays (qPCR, Western blotting) and immunofluorescence imaging. We also offer combination therapy testing to evaluate synergistic effects and reduce the risk of AMR.

Ocular Delivery and Formulation Optimization

Protheragen supports the development and optimization of ocular formulations to enhance therapeutic bioavailability and target tissue penetration. Services include formulation design for topical (eye drops, ointments), intravitreal (injections, implants), and periocular (subconjunctival, retrobulbar) delivery routes. We evaluate formulation performance using in vitro permeation assays (corneal, scleral permeation models), tear film retention testing, and stability analysis under physiological conditions. For nanotherapeutic formulations (lipid nanoparticles, nanogels, dendrimers), we assess particle size, zeta potential, encapsulation efficiency, and release kinetics. In vivo distribution studies measure therapeutic concentrations in target ocular tissues (cornea, vitreous, retina) and systemic tissues to optimize dosing and minimize off-target exposure.

IND-Enabling Safety and Toxicology Assessment

We conduct comprehensive preclinical safety studies to support IND submissions, adhering to Good Laboratory Practice (GLP) standards and regulatory guidelines. Ocular toxicology assessments include local irritation testing (Draize test, corneal opacity scoring), histopathological analysis of ocular tissues, and evaluation of inflammatory responses (cytokine profiling, immune cell infiltration). Systemic toxicity testing measures organ function, hematological parameters, and body weight changes to assess overall safety. For antimicrobial therapies, we evaluate AMR development using serial passage assays and assess off-target effects on commensal ocular microbiota. All studies generate detailed reports with statistically robust data to support regulatory review and clinical trial design.

Types of Infectious Ophthalmic Diseases

Our Therapeutics Development Solutions

Protheragen, a renowned leader in the field of ophthalmology, has built a comprehensive suite of services to address the growing challenge of infectious ophthalmic diseases. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.

References

• Lu, Louise J., and Ji Liu. "Focus: microbiome: human microbiota and ophthalmic disease." The Yale journal of biology and medicine 89.3 (2016): 325.
• Clare Gerry, John H. Kempen, and Carlos Pavésio. "Infectious eye disease in the 21st century—an overview." Eye (2024): 1-14.