RETINAL

Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review article provides a critical discussion of retinal drug delivery, particularly from the pharmacokinetic point of view. This article does not include an extensive review of drug delivery technologies, because they have already been reviewed several times recently. Instead, we aim to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment. This review is based on the literature and unpublished data from the authors' laboratory.

Drug-induced retinal toxicity can occur from the use of systemic, intravitreal, or topical medications. Despite the presence of the blood-ocular barrier, the retina is vulnerable to toxic effects of systemic medications leading to dysfunction and retinal degeneration. These toxicities can be categorized as damage to the retinal pigment epithelium (RPE) and photoreceptor complex, vascular damage, ganglion cell or optic nerve damage, cystoid macular edema, crystalline retinopathy, uveitis, changes in color vision and electroretinography (ERG), and other miscellaneous effects.

Pan-retinal photocoagulation (PRP) is the mainstay of treatment for proliferative diabetic retinopathy (PDR), reducing the risk of severe vision loss. Pain poses a potential obstacle to effective laser delivery and patient compliance. Therefore, implementing pain relief strategies can enhance both treatment efficacy and patient comfort. A systematic review and meta-analysis. We conducted a systematic review and meta-analysis according to PRISMA guidelines. The PubMed, Embase and Cochrane Central Register of Controlled Trials databases were searched for randomized controlled trials (RCTs) that enrolled patients undergoing PRP due to DR and compared analgesics or non-steroidal anti-inflammatory drugs (NSAID) to placebo. Pain was evaluated with the visual analogue scale. The version 2 of the Cochrane Collaboration's Risk of Bias in Randomized Controlled Trials tool and its version for crossover trials were used to assess the risk of bias. The Grading of Recommendations, Assessment, Development, and Evaluation tool was used to measure the certainty of evidence. A total of 13 studies were included, comprising 1404 eyes from RCTs, nine of which were crossover. Patients who were administered analgesia reported a significantly lower pain sensitivity compared to those who received placebo (Standardized mean difference [SMD] -0.38; 95% confidence interval [CI] -0.58, -0.17; P < .01; I 2 = 69%). Subgroup analysis of systemic administration of analgesics/NSAIDs (metamizole, Entonox, acetaminophen, ibuprofen, caffeine, mefenamic acid, intramuscular ketorolac tromethamine, and potassium diclofenac) also showed a statistically significant reduction in pain when compared to placebo (SMD -0.28; 95% CI -0.50, -0.07; P < .01; I 2 = 43%). Exclusive eye drops administration (ketorolac tromethamine 0.5% and sodium diclofenac 0.1%) also showed a significant difference in pain sensitivity (SMD -0.46; 95% CI -0.88, -0.05; I 2 = 83%), however with a more significant heterogeneity. The results of this meta-analysis including over 1000 patients demonstrated that the use of analgesics significantly reduced pain sensitivity during PRP, and systemic analgesia is potentially better than topical administration when compared to placebo.

Intravitreal injections remain the standard for treating common retinal diseases including age-related macular degeneration (AMD), diabetic macular edema (DME) and diabetic retinopathy. However, frequent administration creates significant treatment burden due to limited drug half-life and the chronic nature of these conditions. This review summarizes emerging drug delivery techniques and therapies for retinal disease that have achieved FDA approval within the past five years or have advanced to Phase 3 development, including intravitreal sustained-release platforms and alternative delivery routes (suprachoroidal, subretinal, topical, and subcutaneous). Specific innovations discussed include the ranibizumab port delivery system, EYP-1901 (Duravyu, vorolanib implant), KSI-301 (tarcocimab tedromer), KSI-501, OTX-TKI (Axpaxli, axitinib implant), 4D-150, revakinagene taroretcel-lwey (Encelto, NT-501, encapsulated cell therapy), Xipere (triamcinolone acetonide injectable suspension), AU-011 (belzupacap sarotalocan targeted delivery), ABBV-RGX-314, elamipretide, and OCS-01 (high concentration dexamethasone). Promising innovations include sustained-release intravitreal implants, topical and subcutaneous delivery systems, and targeted methods like suprachoroidal and subretinal injections, each with unique advantages and limitations. Challenges include overcoming the blood-retinal barrier, surgical complications with implantable devices, and ensuring patient adherence. Advances in smart delivery systems, drug formulations, and predictive models, alongside interdisciplinary collaboration, will be crucial in achieving personalized, effective, and sustainable retinal therapies.

Genetic testing is a medical test that studies human DNA to discover genetic changes or mutations that could lead to genetic disease. Genetic testing is performed on samples of DNA that can be obtained from blood, hair, skin, saliva, amniotic fluid, or other tissues. The test results are then sent in writing to the doctor or the genetic counsellor for discussion with the patient and the family.

Novel methods of ophthalmic drug delivery are being developed to facilitate treatment of a variety of eye diseases. Pharmaceuticals administered intravitreally are able to bypass the blood-ocular barrier to achieve constant therapeutic levels in the eye, while minimizing systemic side effects. Sustained-release intravitreal implants are being developed to enhance further the intravitreal route of administration. Liposomes, microscopic vesicles with a membrane-like lipid bilayer surrounding an aqueous compartment, are being developed to incorporate a wide variety of drug molecules, proteins, nucleotides, and even plasmids giving them great potential for use in ophthalmology. Biodegradable scleral plugs containing pharmaceuticals have the advantage of biodegradability and the ability to fit in a relatively small diameter of 1 mm. Conjugate drugs, which are covalently linked, decrease drug solubility, which increases their half-life and also limits the amount of active drug present at a given time. Viral vectors have been investigated in the delivery of genetic material to the posterior segment of the eye. Retrovirus, adenovirus, adenoma-associated virus, herpes virus, and lentivirus have been investigated for gene transfer to the retina. Finally, iontophoresis, a method of drug delivery typically involving the application of low electric currents to drive molecules across barriers, such as skin, is being explored for ophthalmic applications.

A female toddler clinically diagnosed with hand, foot and mouth disease (HFMD) was referred by the treating paediatrician, with acute-onset painless diminution of vision for 3 days. She had papulomacular skin rashes and was unable to follow the light stimulus at presentation. On fundus evaluation, bilateral asymmetrical (left eye more severe than the right eye) multifocal full-thickness necrotising retinitis, occlusive haemorrhagic retinal vasculitis, optic disc pallor and left eye exudative retinal detachment (eRD) were noted. Due to the background of HFMD and unexpected prompt response of intravitreal and systemic corticosteroids, a preliminary diagnosis of bilateral presumed enterovirus-associated retinopathy was established. The patient showed a favourable response to a weekly taper of oral steroids for the next 3 months. The retinitis, vasculitis and eRD were resolved with widespread retinal pigment epithelium (RPE) atrophy.HFMD with retinopathy secondary to presumed enterovirus infection, though rare, can present with extensive RPE and optic disc atrophy despite administration of oral corticosteroids.

We report a rare case of bilateral acute retinal pigment epitheliitis (ARPE) documented using multimodal imaging, with detailed sequential optical coherence tomography (OCT) findings. A woman in her 30s presented with acute bilateral visual deterioration without prodromal symptoms. Fundus examination revealed yellowish-white lesions localized to the fovea in both eyes. OCT demonstrated dome-shaped hyperreflective lesions with disruption of the ellipsoid zone (EZ) and interdigitation zone (IZ). OCT angiography, fluorescein angiography, and indocyanine green angiography showed no significant abnormalities. Based on these findings, bilateral ARPE was diagnosed. Given the bilateral visual impairment, topical betamethasone sodium phosphate was initiated to facilitate early recovery. Sequential OCT demonstrated gradual restoration of the outer retinal layers, with recovery of the external limiting membrane, followed by the IZ and EZ. Best-corrected visual acuity improved to 1.0 in both eyes within two months, and near-complete anatomical resolution was confirmed by three months. No recurrence was observed after treatment cessation. This case highlights the rare bilateral presentation of ARPE and demonstrates the value of OCT in monitoring layer-by-layer recovery of the outer retina, while emphasizing the importance of differentiating it from other white dot syndromes.

Sports-related ocular trauma is an important cause of preventable visual morbidity, particularly in contact sports such as football (soccer). Although many injuries initially present with mild anterior segment findings, significant posterior segment pathology may coexist and can be easily overlooked. We report the case of a 17-year-old male football player who presented with left eye pain, blurred vision, and periorbital bleeding following blunt ocular trauma during a football match. Examination revealed traumatic mydriasis with anterior uveitis, subconjunctival hemorrhage with conjunctival laceration and exposed Tenon's tissue, as well as commotio retinae with a peripheral horseshoe-shaped retinal tear. No retinal detachment was identified. The patient underwent prompt laser retinopexy and received topical anti-inflammatory and antibiotic therapy, resulting in favorable anatomical and visual outcomes. This case highlights the importance of maintaining a high index of suspicion in sports-related ocular trauma, as relatively subtle anterior segment findings may mask significant posterior segment injury. Careful and systematic anterior and posterior segment examination, including peripheral retinal evaluation, is essential to avoid missing sight-threatening complications and to ensure timely intervention.

Diabetic retinal disease remains a leading cause of vision loss, with current treatment limited by frequent injections and poor adherence. Ongoing clinical trials are evaluating topical therapies, sustained delivery systems, and gene therapy as alternatives to current gold standard treatments. The field is shifting toward earlier, more personalized, and more durable disease-modifying strategies.

Secondary full-thickness macular holes (sFTMHs) are rare complications following pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). Although surgical repair is standard, spontaneous closure occurs in a minority of cases. This report describes a case of spontaneous sFTMH closure and reviews the literature to elucidate associated factors and mechanisms. We present a case of a 33-year-old male who developed a sFTMH after silicone oil removal following PPV for RRD. Additionally, a comprehensive PubMed literature search identified published cases of spontaneous sFTMH closure after RRD repair. The patient's sFTMH closed spontaneously within three months, accompanied by improved visual acuity. A review of over 30 published cases reveals distinct pathogenic and resolution factors. Hole formation is driven by postoperative tangential traction from epiretinal membranes (ERM), cystoid macular edema (CME), surgical trauma, and inflammation, with high-altitude exposure as a notable environmental risk. Conversely, spontaneous closure is favored by a smaller hole diameter and the presence of epiretinal proliferation (EP) which may act as a scaffold for glial bridging, and often coincides with CME resolution, potentially accelerated by topical therapy. Mechanistically, closure is mediated by glial proliferation and tissue apposition under persistent epiretinal traction, combined with intraretinal fluid resorption, leading to variable restoration of the retinal laminar structure. Spontaneous closure of sFTMHs after RRD surgery is a recognized phenomenon. For selected patients with small, minimally symptomatic holes associated with edema or EP, initial management with observation, potentially supplemented by topical therapy, is a viable strategy before considering surgery.

To describe the long-term clinical course of Enhanced S-cone Syndrome (ESCS) in three siblings carrying the same NR2E3 variant, and to report therapeutic outcomes of choroidal neovascularization (CNV) and cystic macular changes during a 12-year follow-up from early childhood. This is a retrospective observational family case with literature review. Three siblings were examined periodically over 12 years beginning in early childhood. Clinical evaluation included best corrected visual acuity (BCVA), cycloplegic refraction, multimodal imaging. CNV was treated with intravitreal ranibizumab, while cystic macular changes were managed with topical carbonic anhydrase inhibitors (CAIs). The three siblings shared a homozygous splice site variant (c.119-2 A > C) in the NR2E3 gene and ERG showed ESCS pathognomonic features. In the eldest brother, acute onset esotropia secondary to visual impairment caused by CNV represented the first clinical manifestation. Following the onset of night blindness between ages 11 and 14, the older brother and sister developed macular cystic changes; however, topical CAIs were ineffective. Notably, they maintained stable visual acuity over a 12-year observation period. This family report underscores the clinical variability in ESCS and suggests that the visual acuity of young patients with ESCS remains stable, even in the presence of macular schisis. CNV was successfully treated with two intravitreal injections of ranibizumab, whilst topical CAIs proved ineffective for treating cystic patterns. Additional long-term studies are required to better understand the natural history of ESCS and improve therapeutic strategies.

West Nile virus (WNV) infection is a recognized cause of neuroinvasive disease and chorioretinitis, typically reported in endemic regions and often associated with positive IgM serology. However, atypical presentations with discordant serology can occur, particularly in non-endemic settings, posing diagnostic challenges. A 58-year-old woman developed acute encephalitis and bilateral panuveitis shortly after travel to a non-endemic region. Serum and cerebrospinal fluid testing showed positive WNV IgG and negative IgM. Multimodal retinal imaging revealed the coexistence of inactive-appearing chorioretinal scars and active full-thickness retinitis, with characteristic wedge-shaped and linear lesion patterns. Fundus autofluorescence, fluorescein angiography, indocyanine green angiography, and optical coherence tomography allowed differentiation of lesions with varying morphology and stages of activity. Although these findings do not confirm viral relapse or reactivation, they suggest prior infection with possible delayed or recurrent ocular and central nervous system involvement. Systemic and topical corticosteroid therapy resulted in rapid clinical and imaging improvement. This case highlights the diagnostic value of multimodal imaging in suspected WNV chorioretinitis and underscores the limitations of serology alone. Atypical serological profiles in non-endemic settings require careful interpretation, and multimodal imaging may provide critical insights into disease activity and staging.

This study aimed to identify baseline prognostic factors associated with visual field (VF) recovery in patients with non-arteritic anterior ischemic optic neuropathy (NAION). This retrospective study included 38 patients (41 eyes) diagnosed with NAION. VF recovery was defined as an improvement of ≥3 dB in mean deviation (MD) at 3 months. Baseline demographic characteristics, systemic vascular risk factors, visual function tests, and retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT) were analyzed. Eleven eyes (26.8%) were classified as the recovery group. Compared with the non-recovery group, the recovery group had significantly better baseline best-corrected visual acuity (BCVA) (P = 0.034) and lower glycated hemoglobin levels (P = 0.033). Baseline VF impairment was significantly less severe in the recovery group, with higher MD (P = 0.049) and visual field index (VFI) values (P = 0.014). No significant association was observed between topical eye drop treatment, including brimonidine and netarsudil, and visual field recovery (p = 0.723). Baseline BCVA strongly correlated with BCVA at 1, 3, and 6 months (all P < 0.001). Multivariate analysis confirmed that better baseline MD (P = 0.041) and higher VFI (P = 0.036) were independently associated with VF recovery. However, RNFL thickness measured at initial visit by OCT did not reliably predict recovery. These findings highlight that baseline functional status remain as the most important predictor of visual field recovery in NAION.

Primary open-angle glaucoma (POAG) is rarely recognized in large felids, yet it may cause severe vision loss and chronic pain. This case report presents the ophthalmological evaluation of a four-year-old Siberian tiger ( Panthera tigris altaica ) maintained under human care that exhibited signs of visual impairment and altered sensorium. Under neuroleptic analgesia, clinical findings included bilateral convergent strabismus, persistent mydriasis, pathologically elevated intraocular pressure (48-52 mmHg), extensive map-like retinopathy, and focal retinal degeneration, supporting a diagnosis of advanced-stage bilateral POAG with irreversible vision loss. Pupillary light reflexes were absent, while fluctuations in pupil size were attributed to ketamine. Although medical and surgical options used in domestic cats may be applicable to non-domestic felids, frequent topical treatment was impracticable and unsafe, vision-preserving surgery was no longer indicated, and advanced diagnostics and specialist ophthalmic surgery were unavailable on site. The therapeutic goal was therefore shifted from vision preservation to long-term pain surveillance and welfare maintenance, including housing adaption and a defined threshold for humane euthanasia. Two types of neurological episodes were also documented as secondary findings; however, their causal relationship with the ocular disease could not be established without advanced neuroimaging. This case highlights the need for accessible on-site or referral-based ophthalmic diagnostics and surgical capacity in zoo settings.

Listeria monocytogenes is a rare ocular pathogen, and posterior segment infection is particularly uncommon. When it involves the retina, its presentation may overlap with viral hypertensive uveitis or necrotizing viral retinitis, especially in eyes with unilateral ocular hypertension, iris atrophy, and chronic recurrent inflammation. This diagnostic overlap may delay recognition of an unusual bacterial cause. A 23-year-old male presented with progressive visual loss in the left eye after a five-year history of recurrent unilateral ocular redness and previously documented marked ocular hypertension. Examination revealed panuveitis with patchy iris stromal atrophy, pigment dispersion, vitreous inflammation, old peripapillary chorioretinal scars, and an active necrotizing chorioretinal lesion involving the macula, associated with retinal hemorrhage and a secondary macular hole. The initial impression was viral hypertensive uveitis with necrotizing chorioretinitis. Aqueous PCR for herpes simplex virus, varicella-zoster virus, and cytomegalovirus was negative, while bacterial multi-nested PCR detected L. monocytogenes. After oral and topical moxifloxacin were added to anti-inflammatory treatment, active intraocular inflammation had clinically resolved by 30 days, the necrotizing chorioretinal lesion evolved into an inactive scar, and the secondary macular hole progressively decreased in size before closing spontaneously. No systemic illness or immunocompromising condition was identified. This case expands the spectrum of ocular listeriosis in the posterior segment and highlights L. monocytogenes as a rare cause of necrotizing chorioretinitis that may masquerade as viral hypertensive uveitis. Aqueous PCR can be decisive when the presentation is atypical or when the response to initial empirical treatment is incomplete. To the best of our knowledge, this is the first reported case of PCR-confirmed L. monocytogenes necrotizing chorioretinitis complicated by secondary macular hole formation.

To develop and validate a novel set of ocular-centric diagnostic criteria for Behçet's uveitis (BU). A case-control study was designed to develop the BU-specific diagnostic criteria (BU-SDC). The International Criteria for Behçet's Disease were adopted as the reference standard for diagnostic performance evaluation. The ocular findings of BU-SDC were weighted as two points for vitreous cells or haze and retinal vasculitis identified by fluorescein fundus angiography, respectively, and one point for anterior cell-flare dissociation, sterile hypopyon, diffuse retinal atrophy, optic nerve atrophy, superficial retinal infiltrates, retinal haemorrhages, retinal vascular sheathing and retinal ghost vessels, respectively. The systemic features, including recurrent oral ulceration, multiform skin lesions and genital ulceration were weighted as 4 points, 3 points and 2 points, respectively. Primary assessment was based on ocular features alone. An ocular score ≥5 supported a BU diagnosis in patients without signs of granulomatous uveitis or evidence of sarcoidosis or syphilis. For patients with ocular score <5 but high clinical suspicion (the presence of one or more characteristic ocular signs, including vitreous cells or haze, retinal vasculitis identified by fluorescein fundus angiography, superficial retinal infiltrates or retinal vascular sheathing), a secondary assessment incorporating systemic variables was applied, and a combined score ≥5 supported diagnosis. Validation in the independent cohort showed that the area under the receiver operating characteristic curve for BU-SDC (0.954) significantly outperformed the International Study Group criteria (0.911; p<0.01) and the Standardization of Uveitis Nomenclature (0.881; p<0.01) criteria. The BU-SDC provides a validated ocular-centric diagnostic framework for BU, prioritising ocular signs while retaining flexibility through selective systemic integration.

High-density stretchable pixelated electronics that conform to complex, non-developable surfaces are key enablers of next-generation robotic vision systems, skin-mountable sensors and wearable electronics. Existing strategies for stretchable pixelated device arrays-such as buckling mechanics, pop-up structures, serpentine interconnects and kirigami designs-have offered partial solutions. However, a strategy that simultaneously achieves high device performance, stretchability, fill factor and integration density has remained elusive. Here we present a next-generation platform for stretchable pixelated electronics that integrates high-performance single-crystalline silicon pixels with finely patterned liquid metal interconnects on ultrathin elastomeric substrates. We developed a monolithic microfabrication strategy that enables customizable, densely packed and mechanically compliant pixelated device arrays. Using this platform, we demonstrate shape-reconfigurable imaging devices that achieve superb fill factors of up to 81% and a biaxial stretchability of 100%. We also present a human-eye-inspired robotic vision system with tunable focus and a skin-mountable lens-free imaging system. The complementary operation of retinal and epidermal imaging systems enables multiscale visual acquisition and depth sensing.