Injections in the back of the eye: The why, the what and when to worry.

BACKGROUND: Many Australians, particularly the elderly, suffer from eye diseases that require treatment with regular injections given into the eye. These injections can result in complications, some of which can be vision threatening. OBJECTIVE: To summarise some of the more common reasons for intraocular injection, as well as some common and/or more serious complications of intraocular injection that might present to general practitioners. DISCUSSION: Intraocular injection is an increasingly common means of treatment for a range of eye conditions. Serious complications, although rare, often require acute intervention to achieve the best outcomes, and timely referral of patients with worrying symptoms is important to achieve optimum patient care.

Intracameral Injection in Rats with Low Risk of Adverse Effects.

Intracameral injection is a standard administration routine in ophthalmology. The application of intracameral injection in rodents for research is challenging due to the limiting dimensions and anatomy of the eye, including the small aqueous humor volume, the lens curvature, and lens thickness. Potential damage during intracameral injections introduces adverse effects and experimental variability. This protocol describes a procedure for intracameral injection in rats, allowing precision and reproducibility. Sprague-Dawley rats were used as experimental models. Since the lens position in rats protrudes into the anterior chamber, injecting from the periphery, as done in humans, is unfavorable. Therefore, an incision is created in the central corneal region using a 31 gauge 0.8 mm stiletto blade to form a self-sealing tunnel into the anterior chamber. An incision at an angle close to the flat allows to create a long tunnel, which minimizes the loss of aqueous humor and shallowing of the anterior chamber. A 34 gauge nanoneedle is inserted into the tunnel for injection. This enables penetration with minimal friction resistance and avoids touching the lens. Injection of trypan-blue allows visualization by slit microscopy the presence of the dye in the anterior chamber and exclude leakage. Bioavailability to the corneal endothelial layer is demonstrated by injection of Hoechst dye, which stained the nuclei of corneal endothelial cells after injection. In conclusion, this protocol implements a procedure for accurate intracameral injection in rats. This procedure may be used for intracameral delivery of various drugs and compounds in experimental rat models, increasing the efficiency and reproducibility of ophthalmic research.

Sharper vision, steady hands: can robots improve subretinal drug delivery? Systematic review.

Subretinal injection (SI) is a novel drug delivery method, directly to retina for treatment of various eye disease. However, manual injection requires surgical experience and precision due to physiological factors. Robots offer solution to this issue, by reducing hand tremor and increased accuracy. This systematic review analyzes current status on robot-assisted SI compared to conventional techniques. Systematic search across 5 databases was conducted to identify studies comparing manual and robot-assisted SI procedures. Extracted data included robotic systems, complications, and success rates. Four studies, including one human trial, two ex vivo porcine eye studies, and one artificial eye model study were included in the synthesis. The findings show early advantages of robot-assisted SI. Compared to traditional interventions, robot procedures result in reduced tremor, what potentially lowers the risk of complications, including retinal tears and reflux. The first in-human randomized trial showed encouraging results, with no significant differences in surgical times or complications between robot-assisted and manual SI. However, major limitation of robot-assisted procedures is longer procedure time. Robot-assisted SI holds promise by offering increased precision and stability, reducing human error and potentially improving clinical outcomes. Challenges include cost, availability, and learning curve. Overall, early stage of robot-assisted SI suggests advantages in precision, complication reduction, and potentially improved drug delivery. Further research in human randomized trials is needed to fully assess its full-scale clinical application.

Subconjunctival adalimumab for treatment of dry eye disease in Sjögren's syndrome / Tratamento de olho seco com adalimumabe subconjuntival em pacientes portadores da síndrome de Sjögren

ABSTRACT Objective To describe the use of subconjuctival administration of the anti-tumor necrosis factor agent adalimumab for treatment of dry eye in patients with Sjögren's syndrome, and to investigate conjunctival healing. Methods Prospective, nonrandomized, noncomparative interventional case series including consecutive patients with Sjögren's syndrome and dry eye disease treated with subconjunctival adalimumab, who were refractory to conventional treatment. Patients with infectious ocular surface involvement or structural changes in the tear pathway or eyelids were excluded. Data recorded included age, sex, lissamine green staining pattern, Schirmer test results, intraocular pressure, conjunctival mobility, tear break up time and findings of biomicroscopic evaluation, following fluorescein dye instillation. The Ocular Surface Disease Index questionnaire validated for the Portuguese language was used for subjective assessment of patients. Results Eleven eyes of eight patients were studied. Mean patient age was 53±13.4 years. Patients were treated with subconjunctival injection of 0.03 mL of adalimumab and followed for 90 days thereafter. There were no statistically significant objective improvement (objective tests results; p>0.05) and no statistically significant changes in intraocular pressure (p=0.11). Questionnaire responses revealed a significant improvement in ocular symptoms (p=0.002). Conclusion Based on the Ocular Surface Disease Index questionnaire, subconjunctival administration of adalimumab improved dry eye symptoms. However, objective assessments failed to reveal statistically significant improvements.

RESUMO Objetivo Descrever o uso subconjuntival do antifator de necrose tumoral adalimumabe para o tratamento do olho seco em pacientes com síndrome de Sjögren e avaliar a cicatrização conjuntival. Métodos Série de casos intervencionista com desenho prospectivo, não randomizado, não comparativo. O medicamento adalimumabe foi aplicado em região subconjuntival em pacientes com síndrome de Sjögren e olho seco que eram resistentes a outras terapias convencionais. Pacientes com patologias oculares de origem infecciosa ou com alterações estruturais nas vias lacrimais e pálpebras foram excluídos do estudo. Os dados coletados incluíram idade, sexo, teste com lisamina verde, teste de Schirmer, pressão intraocular, mobilidade conjuntival, teste de ruptura do filme lacrimal, e avaliação biomicroscópica com colírio de fluoresceína. Além disso, o questionário Ocular Surface Disease Index validado para a língua portuguesa foi aplicado com objetivo de avaliar subjetivamente a resposta dos pacientes ao tratamento. Resultados Onze olhos de oito pacientes foram estudados. A idade média dos pacientes foi de 53±13,4 anos. A dose aplicada de adalimumabe subconjuntival foi de 0,03mL, e a duração do seguimento foi de 90 dias após a injeção. Não houve melhora estatisticamente significativa nos testes objetivos (todos apresentaram p>0,05). A pressão intraocular também não sofreu variações estatisticamente significativas (p=0,11). Entretanto, por meio do questionário, foi registrada melhora significativa dos sintomas oculares (p=0,002). Conclusão O uso do adalimumabe subconjuntival melhorou os sintomas de olho seco, avaliados por meio do questionário Ocular Surface Disease Index, mas não houve melhora estatisticamente significativa na avaliação objetiva.

Suprachoroidal delivery of bevacizumab in rabbit in vivo eyes: Rapid distribution throughout the posterior segment.

PURPOSE: To test the in-vivo bio-distribution and safety of bevacizumab delivery into the suprachoroidal space (SCS) using a novel injection system in a large eye model. METHODS: Bevacizumab (1.25 mg) was injected into the vitreous (IVT, 50 µL, n = 12) or the SCS, (150 µL, n = 37) of live rabbits. Immunofluorescence and ELISA were used to assess bevacizumab distribution. Intraocular pressure (IOP) measurements, SD-OCT and fundus imaging, electroretinogram, and histology analysis were performed for safety assessment. RESULTS: Bevacizumab was observed throughout the choroid layers up to the retinal pigment epithelium (RPE), within 1 h following SCS injection. The Cmax of bevacizumab in the retina/choroid was 1043 ± 597 µg/gr tissue (mean ± standard error), 40-fold higher than in IVT injected eyes (p = 0.0339). One day following SCS injection, bevacizumab was detected throughout the posterior pole with a two-fold lower concentration. One week post-SCS injection, bevacizumab concentration in the retina/choroid dropped to 2.36 ± 1.32 µg/gr tissue (p = 0.034 vs. 1 h), with a half-life of 20 h. No suprachoroidal blebs, retinal detachment, hemorrhages, inflammation or changes in retinal function were observed up to 2 months following SCS injection. Elevated IOP (+16 mmHg) was observed two minutes post-SCS injection and spontaneously returned to baseline levels within 10 minutes. CONCLUSIONS: The novel injection system enabled a minimally invasive, safe, and consistent delivery of bevacizumab with rapid distribution throughout the choroid layers up to the RPE in large eyes. Large volumes of anti-angiogenic are delivered in close proximity to the retina due to the high volume distribution.

Intraocular iron injection induces oxidative stress followed by elements of geographic atrophy and sympathetic ophthalmia.

Iron has been implicated in the pathogenesis of age-related retinal diseases, including age-related macular degeneration (AMD). Previous work showed that intravitreal (IVT) injection of iron induces acute photoreceptor death, lipid peroxidation, and autofluorescence (AF). Herein, we extend this work, finding surprising chronic features of the model: geographic atrophy and sympathetic ophthalmia. We provide new mechanistic insights derived from focal AF in the photoreceptors, quantification of bisretinoids, and localization of carboxyethyl pyrrole, an oxidized adduct of docosahexaenoic acid associated with AMD. In mice given IVT ferric ammonium citrate (FAC), RPE died in patches that slowly expanded at their borders, like human geographic atrophy. There was green AF in the photoreceptor ellipsoid, a mitochondria-rich region, 4 h after injection, followed later by gold AF in rod outer segments, RPE and subretinal myeloid cells. The green AF signature is consistent with flavin adenine dinucleotide, while measured increases in the bisretinoid all-trans-retinal dimer are consistent with the gold AF. FAC induced formation carboxyethyl pyrrole accumulation first in photoreceptors, then in RPE and myeloid cells. Quantitative PCR on neural retina and RPE indicated antioxidant upregulation and inflammation. Unexpectedly, reminiscent of sympathetic ophthalmia, autofluorescent myeloid cells containing abundant iron infiltrated the saline-injected fellow eyes only if the contralateral eye had received IVT FAC. These findings provide mechanistic insights into the potential toxicity caused by AMD-associated retinal iron accumulation. The mouse model will be useful for testing antioxidants, iron chelators, ferroptosis inhibitors, anti-inflammatory medications, and choroidal neovascularization inhibitors.

Ocular Delivery of Predatory Bacteria with Cryomicroneedles Against Eye Infection.

The development of potent antibiotic alternatives with rapid bactericidal properties is of great importance in addressing the current antibiotic crisis. One representative example is the topical delivery of predatory bacteria to treat ocular bacterial infections. However, there is a lack of suitable methods for the delivery of predatory bacteria into ocular tissue. This work introduces cryomicroneedles (cryoMN) for the ocular delivery of predatory Bdellovibrio bacteriovorus (B. bacteriovorus) bacteria. The cryoMN patches are prepared by freezing B. bacteriovorus containing a cryoprotectant medium in a microneedle template. The viability of B. bacteriovorus in cryoMNs remains above 80% as found in long-term storage studies, and they successfully impede the growth of gram-negative bacteria in vitro or in a rodent eye infection model. The infection is significantly relieved by nearly six times through 2.5 days of treatment without substantial effects on the cornea thickness and morphology. This approach represents the safe and efficient delivery of new class of antimicrobial armamentarium to otherwise impermeable ocular surface and opens up new avenues for the treatment of ocular surface disorders.

In utero intraocular AAV injection for early gene expression in the developing rodent retina.

The visual system is the best system to study activity-dependent sensory circuit development. The connections from the retina to the dorsal lateral geniculate nucleus, the retinogeniculate connections, undergo extensive remodeling during early postnatal life. Thus, techniques that allow the expression of transgenes early in the developing retina are essential to study visual system development. Here, we describe a protocol to express genes-of-interest in the developing mouse retina via in utero intraocular adeno-associated virus injections. For complete details on the use and execution of this protocol, please refer to Yasuda et al. (2021).

Laser-induced choroidal neovascularization: A case report and some reflection on animal models for age-related macular degeneration.

RATIONALE: Laser induced maculopathy includes retinal photoreceptor disruption, macular hole, macular hemorrhage, and rarely choroidal neovascularization (CNV). Here we report a case of laser induced CNV that was treated by intravitreal anti-vascular endothelial growth factor (VEGF) injection and resulted in visual improvement and CNV resolution during 1-year follow up. In addition, the case of laser induced CNV treated with intravitreal anti-VEGF injections are reviewed for the first time in literature. PATIENT CONCERNS: A 7-year-old boy presented to our department with blurred vision in his right eye for 2 months. The symptom immediately happened after the boy staring at the laser beam for a few seconds. Examination of ocular fundus with slit lamp showed yellowish lesion in macula in his right eye. DIAGNOSES: CNV was confirmed by fundus examinations, including color fundus photograph, spectral domain optical coherence tomography, fluorescein angiography, and spectral domain optical coherence tomography angiography. INTERVENTIONS: After the diagnosis of laser induced CNV, intravitreal ranibizumab (LUCENTIS, NOVARTIS) injection was performed. OUTCOMES: After 1 injection of intravitreal ranibizumab, the best corrected visual acuity improved from 20/50 to 30/50 and CNV gradually regressed during 1-year follow up. LESSONS: For young patients with laser induced CNV, intravitreal anti-VEGF injections may be helpful in visual improvement and CNV regression. Moreover, age seems to be a significant factor thus we propose that old animals may be more appropriate for laser induced CNV animal models of age-related macular degeneration.

Activated microglia-induced neuroinflammatory cytokines lead to photoreceptor apoptosis in Aß-injected mice.

Age-related macular degeneration (AMD) is mainly characterized by the progressive accumulation of drusen deposits and loss of photoreceptors and retinal pigment epithelial (RPE) cells. Because amyloid ß (Aß) is the main component of drusen, Aß-induced activated microglia most likely lead to neuroinflammation and play a critical role in the pathogenesis of AMD. However, the relationship between activated microglia-mediated neuroinflammatory cytokines and photoreceptor death has not been clarified. By subretinal injection of Aß42 in mice, we mimicked an inflammatory milieu of AMD to better understand how activated microglia-induced neuroinflammatory cytokines lead to photoreceptor apoptosis in the AMD progression. We demonstrated that subretinal injection of Aß42 induces microglial activation and increases inflammatory cytokine release, which gives rise to photoreceptor apoptosis in mice. Our results were verified in vitro by co-culture of Aß42 activated primary microglia and the photoreceptor cell line 661W. We also demonstrated that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was involved in Aß42-induced microglial activation and inflammatory cytokine release. Overall, our findings indicate that activated microglia-derived neuroinflammatory cytokines could contribute to photoreceptor apoptosis under the stimulation of Aß42. Moreover, this study may provide a potential therapeutic approach for AMD. KEY MESSAGES: Further explore the association between activated microglia-derived neuroinflammatory cytokine secretion and photoreceptor apoptosis under the stimulation of Aß42. Subretinal injection of Aß42 induces the activation of microglia and increases proinflammatory cytokines IL-1ß and COX-2 expression in the retina, which could give rise to the deterioration of visual function and aggravate photoreceptor apoptosis in mice. Primary microglial are activated and the levels of proinflammatory cytokines are increased by Aß42 stimulation, which could increase the apoptosis of photoreceptor cell line 661W in vitro. The p38 MAPK signaling pathway is involved in microglial activation and photoreceptor apoptosis under Aß42 treatment.

Overcoming barriers by local drug delivery with liposomes.

Localized or topical administration of drugs may be considered as a potential approach for overcoming the problems caused by the various biological barriers encountered in drug delivery. The combination of using localized administration routes and delivering drugs in nanoparticulate formulations, such as liposomes, may have additional advantages. Such advantages include prolonged retention of high drug loads at the site of action and controlled release of the drug, ensuring prolonged therapeutic effect; decreased potential for side-effects and toxicity (due to the high topical concentrations of drugs); and increased protection of drugs from possible harsh environments at the site of action. The use of targeted liposomal formulations may further potentiate any acquired therapeutic advantages. In this review we present the most advanced cases of localized delivery of liposomal formulations of drugs, which have been investigated pre-clinically and clinically in the last ten years, together with the reported therapeutic advantages, in each case.

Comparative Pharmacokinetics of Nimodipine in Rat Plasma and Tissues Following Intraocular, Intragastric, and Intravenous Administration.

We investigated the pharmacokinetics of nimodipine (NMD) in rats plasma and tissues following intraocular (io), intragastric (ig), and intravenous (iv) administration at doses of 5.0 mg/kg io and iv and 10.0 mg/kg ig. After a single dose of NMD, plasma, heart, liver, spleen, lung, kidney, and brain samples were collected at the scheduled time points. The concentration of NMD in rat plasma and tissues was determined by high-performance liquid chromatography, and the main pharmacokinetic parameters were calculated and compared. NMD was rapidly absorbed and reached the maximum plasma concentration in approximately 5 min after io administration. The absolute bioavailability after io administration was higher than that after ig administration (40.05% vs. 5.67%). There were significant differences in the tissue distribution of NMD with different administration routes. After io administration, NMD was distributed more in the lung, spleen, and brain tissues, and less in the kidney. The maximum drug concentration after io administration in the heart, liver, spleen, lung, kidney, and brain was 1.00, 0.47, 2.02, 1.47, 0.22, and 5.79 times higher than that after via ig administration, and the area under the curve value was 0.59, 0.78, 1.71, 1.84, 0.25, and 4.59 times greater, respectively. Nimodipine appears to achieve systemic effects via io administration. Compared with ig, io administration could significantly increase NMD distribution in the brain tissue, indicating that NMD could be delivered to the brain via io administration.

Pain during pars plana vitrectomy following sub-Tenon versus peribulbar anesthesia: A randomized trial.

PURPOSE: To compare pain during pars plana vitrectomy (PPV) following topical lidocaine jelly and sub-Tenon anesthesia versus peribulbar anesthesia. METHODS: Prospective, single-center, randomized study. Patients scheduled for PPV for macular hole (MH) or epiretinal membrane (ERM) at the Retina and Vitreous Section of the Department of Ophthalmology, Ribeirão Preto Medical School, University of São Paulo were randomly assigned to one of two groups in a 1:1 allocation ratio. Patients assigned to Group ST received topical anesthesia with 2% lidocaine jelly followed by sub-Tenon anesthesia with 2-4 ml of 1% ropivacaine. Patients assigned to PB received peribulbar anesthesia with 4-6 ml of 1% ropivacaine. After PPV, patients in both groups were asked to rate the level of pain they felt during the entire procedure (including anesthesia administration and PPV) by pointing at a 0-100 Visual Analogue Pain Scale (VAS). Data regarding demographics, patient characteristics and surgical features were also collected. RESULTS: Fifty-four patients were enrolled in the study (26 in Group ST and 28 in Group PB). Baseline characteristics, including age, gender, and presence of comorbidities, were similar in both groups. The surgery performed was PPV alone in 10 and 14 patients in the ST and PB groups, respectively, and combined phacoemulsification and PPV in 16 and 14 patients in the ST and PB groups, respectively (p = 0.39, Pearson). Surgery duration (mean ± SD minutes) was similar in the two groups (62 ± 12 for ST and 70 ± 20 for PB, p = 0.09, t-Test). No patients needed supplemental topical or intravenous anesthesia during surgery. No sight- or life-threatening complication was observed in either group. VAS score was significantly lower in the ST compared to the PB group (median (interquartile range) was 1 (2.25-0) in the ST group compared to 11.5 (29.75-5) in the PB group, p< 0.0001, Wilcoxon). CONCLUSION: In this study of patients who underwent PPV for MH or ERM, topical followed by sub-Tenon anesthesia was more effective in controlling pain during the whole vitrectomy procedure than peribulbar anesthesia. Compared to peribulbar anesthesia which is administered with a sharp needle, sub-Tenon anesthesia administered with a blunt cannula may be associated with a reduced risk of such adverse events as globe perforation, retrobulbar hemorrhage, and inadvertent injection of anesthesia into the optic nerve sheath.

Investigation of Injection Depth for Subretinal Delivery of Exogenous Glutamate to Restore Vision via Biomimetic Chemical Neuromodulation.

Chemical neuromodulation of the retina using native neurotransmitters to biomimetically activate target retinal neurons through chemical synapses is a promising biomimetic alternative to electrical stimulation for restoring vision in blindness caused by photoreceptor degenerative diseases. Recent research has shown that subretinal chemical stimulation could be advantageous for treating photoreceptor degenerative diseases but many of the parameters for achieving efficacious chemical neuromodulation are yet to be explored. In this paper, we investigated how the depth at which neurotransmitter is injected subretinally affects the success rate, spike rate characteristics (i.e., amplitude, response latency, and time width), and spatial resolution of chemical stimulation in wild-type Long Evans and photoreceptor degenerated S334ter-3 transgenic rat retinas in vitro. We compared the responses to injections of glutamate at the subretinal surface and two subsurface depths near the outer and inner plexiform layers and found that while injections at all depths elicited robust retinal ganglion cell responses, they differed significantly in terms of the spike rate characteristics and spatial resolutions across injection depths. Shallow subsurface injections near the outer plexiform layer evoked the highest spike rate amplitudes and had the highest spatial resolution and success rates, while deep subsurface injections near the inner plexiform layer elicited the shortest latencies and narrowest time widths. Our results suggest that surface injections are suboptimal for subretinal chemical neuromodulation, while shallow subsurface and deep subsurface injections may optimize high spatial and high temporal resolution, respectively. These findings have great significance for the design and development of a potential neurotransmitter-based subretinal prosthesis.

Ocular Intracameral Pharmacokinetics for a Cocktail of Timolol, Betaxolol, and Atenolol in Rabbits.

The mechanisms of drug clearance from the aqueous humor are poorly defined. In this study, a cocktail approach was used to simultaneously determine the pharmacokinetics of three ß-blocker agents after intracameral (ic) injection into the rabbit eyes. Aqueous humor samples were collected and analyzed using LC-MS/MS to determine drug concentrations. Pharmacokinetic parameters were obtained using a compartmental fitting approach, and the estimated clearance, volume of distribution, and half-life values were the following: atenolol (6.44 µL/min, 687 µL, and 73.87 min), timolol (19.30 µL/min, 937 µL, and 33.64 min), and betaxolol (32.20 µL/min, 1421 µL, and 30.58 min). Increased compound lipophilicity (atenolol < timolol < betaxolol) resulted in higher clearance and volume of distributions in the aqueous humor. Clearance of timolol and betaxolol is about 10 times higher than the aqueous humor outflow, demonstrating the importance of other elimination routes (e.g., uptake to iris and ciliary body and subsequent elimination via blood flow).

Providing Optimal Rejuvenation to the Periocular Area Using Botulinum Toxin A Neuromodulators and Hyaluronic Acid Dermal Fillers.

The periorbital area is the first area of the face to show signs of aging. To provide safe and natural looking rejuvenation of the delicate eyelids, and supporting structures, an advanced understanding of anatomy, ideal facial proportions, and the most effective methods for rejuvenation is discussed. Periocular rejuvenation is particularly challenging due to the intricate and delicate anatomy of the periocular area. To ensure safe and successful outcomes, it is crucial that injectors use a global approach when providing treatments and that they consider soft tissue, vasculature, and bone structure of the periocular region before administering treatments for aesthetic rejuvenation. Neuromodulators, specifically botulinum toxin A (BoNT-A), and hyaluronic acid (HA) dermal fillers are 2 nonsurgical treatments frequently used to address signs of aging in the periocular area. The objective of this article is to review different BoNT-A and HA filler treatments and discuss how these treatments can be used for optimal rejuvenation of the periocular area.

Intraocular administration of tetramethylpyrazine hydrochloride to rats: a direct delivery pathway for brain targeting?

The purpose of this study was to compare the pharmacokinetic profile of tetramethylpyrazine hydrochloride (TMPH) in rat plasma and tissues following intravenous (iv), intragastric (ig) and intraocular (io) administration. After io, ig and iv administration of a single dose at 10 mg/kg, tissue and plasma samples drawn from the femoral artery were collected at timed intervals. The concentration of TMPH in the samples was analyzed using high-performance liquid chromatography (HPLC). The area under the concentration-time curve (AUC) and the drug targeting efficiency percentage (DTE(%)) were calculated to evaluate the targeting efficiency of the drug with the three different administration routes. After io administration, TMPH was rapidly absorbed to reach its peak plasma and brain concentration within 5 min. The systemic bioavailability obtained with io administration was greater than that obtained through the ig route (63.22% vs. 16.88%). The AUCt rank order of the iv administration group was AUCkidney >AUCheart >AUCliver >AUCbrain >AUCspleen >AUClung; that of the ig administration group as AUCkidney >AUCliver >AUCheart >AUCspleen >AUCbrain >AUClung; while that of the io administration group was AUCkidney >AUCbrain >AUCheart >AUCliver >AUCspleen >AUClung. The ratio of the AUCbrain value between the io route and iv injection was 1.05, which was greater than that obtained after ig administration (0.30). The DTE after io administration was calculated: brain (165.72%), heart (97.76%), liver (113.06%), spleen (105.31%), lung (163.40%) and kidney (135.31%). The io administration group showed obvious drug transport to the brain. These results indicate that TMPH is rapidly absorbed from the eye into the systemic circulation, and there may be a direct translocation pathway for TMPH from the eye to the brain. Therefore, io administration of TMPH could be a promising alternative to intravenous and oral approaches.

Efficacy of Subconjunctival Injection of Bevacizumab in Regressing Corneal Neovascularisation.

OBJECTIVE: To determine the efficacy of subconjunctival injection of bevacizumab in regressing corneal neovascularisation. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Department of Ophthalmology, Chandka Medical College and Hospital, SMBBMU, Larkana, Pakistan, from October 2015 to March 2016. METHODOLOGY: A total of 95 patients with corneal neovascularisation of more than 3 months' duration and with no history of previous or current anti-VEGF treatment were included in the study. Patients with any other active ocular disease or using any medication were excluded from the study. Subconjunctival injection of bevacizumab 0.05 ml (1.25 mg) was given near the limbus where maximum neovascularisation was seen. The final outcome was assessed after one month of injection; Pre- and post-treatment slit-lamp examination was done and corneal photograph was taken with anterior segment digital camera to see any regression in corneal neovessels from the baseline. RESULTS: Out of the total 95 patients, 62 (65.3%) were males and 33 (34.7%) were females, 18 (18.9%) patients were known cases of diabetes mellitus and 8 (8.4%) had hypertension. Mean age was 38.46 ±10.01 years. Mean duration of corneal neovascularisation was 1.81 ±3.68 years. After subconjunctival injection of bevacizumab, 14.7% patients showed regression in corneal neovascularisation. CONCLUSION: Subconjunctival injection of bevacizumab is a promising modality for treatment of corneal neovascularisation and may be used in adjunct to other therapies.

Optimized Subretinal Injection Technique for Gene Therapy Approaches.

Gene therapy for inherited eye diseases requires local viral vector delivery by intraocular injection. Since large animal models are lacking for most of these diseases, genetically modified mouse models are commonly used in preclinical proof-of-concept studies. However, because of the relatively small mouse eye, adverse effects of the subretinal delivery procedure itself may interfere with the therapeutic outcome. The method described here aims to provide the details relevant to perform a transscleral pars plana virus-mediated gene transfer to achieve an optimized therapeutic effect in the small mouse eye.