Blood-aqueous Barrier Research Articles

Early Immunosuppressive Therapy and Ocular Complications in Pediatric and Young Adult Patients with Non-Infectious Uveitis at a Tertiary Referral Center in Japan

ABSTRACT Purpose To evaluate differences in the incidence of ocular complications among pediatric and young adult patients with non-infectious uveitis receiving immunosuppressive therapy (IMT), according to the time from uveitis onset to IMT initiation in Japan. Methods Patients aged < 20 years exhibiting uveitis treated with IMT (e.g. methotrexate, cyclosporine, infliximab, or adalimumab) were categorized into three groups according to the time from uveitis onset to IMT initiation: ≤6 months, early IMT group; 7 months to 2 years, intermediate IMT group; and ≥ 2 years, late IMT group. The percentage of ocular complications was compared among these groups. Laser flare values were recorded to evaluate disruption of the blood-aqueous barrier (BAB). Results Forty-three patients (84 eyes) who received IMT during the follow-up period were included. Among them, 28 patients (65.1%) experienced ≥ 1 ocular complication, with percentage of 56.0% in the early IMT group, 77.8% in the intermediate group, and 77.8% in the late group. Common complications were cataract (27.4%), posterior synechiae (17.9%), and macular edema (10.7%). The early IMT group did not require surgical intervention. The late IMT group experienced a high percentage of ocular complications despite IMT initiation. The mean laser flare value during follow-up was consistently higher in the late group (113.2 pc/ms) than in the early group (14.4 pc/ms) and intermediate group (28.7 pc/ms). Conclusion In pediatric and young adult patients with chronic non-infectious uveitis, early IMT initiation may prevent permanent breakdown of the BAB, reduce the incidence of ocular complications, and decrease the need for surgical intervention.

Delayed onset Spontaneous Hyphema after OMNI® Surgical System

Minimally invasive glaucoma surgery (MIGS) offers options for glaucoma treatment that have generally improved safety profiles compared with filtering surgery. MIGS vary in design and procedure, but all angle-based MIGS function by bypassing or removing aqueous humor outflow resistance at the level of the trabecular meshwork. This can lower intraocular pressure but also remove the blood-aqueous barrier. Most studies of MIGS report on relatively short-term safety, but awareness of potential long-term complications is critical for optimal patient management. This case report describes a patient with recurrent and refractory delayed onset spontaneous hyphema after OMNI procedure. To the best of our knowledge, this is the first case report describing this complication of the OMNI surgical system.

Magnetically Controlled Intraocular Delivery of Dexamethasone Using Silica-Coated Magnetic Nanoparticles.

Although the number of patients with eye diseases is increasing, efficient drug delivery to the posterior segment of the eyeball remains challenging. The reasons include the unique anatomy of the eyeball, the blood-aqueous barrier, the blood-retina barrier, and drug elimination via the anterior chamber and uveoscleral routes. Solutions to these obstacles for therapeutic delivery to the posterior segment will increase the efficacy, efficiency, and safety of ophthalmic treatment. Micro/nanorobots are promising tools to deliver therapeutics to the retina under the direction of an external magnetic field. Although many groups have evaluated potential uses of micro/nanorobots in retinal treatment, most experiments have been performed under idealized in vitro laboratory conditions and thus do not fully demonstrate the clinical feasibility of this approach. This study examined the use of magnetic nanoparticles (MNPs) to deliver dexamethasone, a drug widely used in retinal disease treatment. The MNPs allowed sustainable drug release and successful magnetic manipulation inside bovine vitreous humor and the vitreous humor of living rabbits. Therefore, controlled drug distribution via magnetic manipulation of MNPs is a promising strategy for targeted drug delivery to the retina.

Anterior Segment Optical Coherence Tomography in Uveitis-Glaucoma-Hyphema Syndrome

ABSTRACT Purpose Uveitis-Glaucoma-Hyphema (UGH) syndrome results from contact between the intraocular lens (IOL) and the iris or ciliary body, leading to uveal structure erosion and blood-aqueous barrier breakdown. Treatment involves various drugs, with IOL removal often being necessary. Diagnosis relies on clinical signs, but imaging techniques like ultrasound biomicroscopy (UBM) or anterior segment optical coherence tomography (AS-OCT) are crucial. AS-OCT accurately depicts IOL position and potential contact, emerging as a primary alternative to UBM in the diagnosis. Our study aimed to correlate AS-OCT findings with clinically detectable iris atrophy in pseudophakic patients with IOL-iris chafing and UGH syndrome. Methods The study retrospectively analyzed patients diagnosed with UGH syndrome presenting at the Ocular Immunology Unit of Reggio Emilia, Italy, from January 2019 to August 2023. Patients’ data were collected. Ophthalmological exams and imaging were performed. The peephole sign in AS-OCT images was evaluated. Statistical analyses were conducted, with a significance level of p ≤ 0.05. Results The study reviewed 22 eyes of 22 patients with UGH syndrome. Four eyes were excluded, leaving 18 patients (8 females, 10 males). Common misdiagnoses included idiopathic anterior uveitis (55.5%) and herpetic anterior uveitis (16.7%). All patients had iris transillumination defects, mostly focal (77.8%). AS-OCT revealed IOL chafing in all the eyes, with peephole sign correlation. More peephole signs occurred with IOL in the sulcus (p-value = 0.08). Conclusion The study recommends AS-OCT for UGH syndrome confirmation and UBM when IOL-iris chafing is not observed on AS-OCT scans.

Rat Model of Type 2 Diabetes Mellitus Recapitulates Human Disease in the Anterior Segment of the Eye

Changes in the anterior segment of the eye due to type 2 diabetes mellitus (T2DM) are not well-characterized, in part due to the lack of a reliable animal model. This study evaluated changes in the anterior segment, including crystalline lens health, corneal endothelial cell density, aqueous humor metabolites, and ciliary body vasculature, in a rat model of T2DM compared with human eyes. Male Sprague-Dawley rats were fed a high-fat diet (45% fat) or normal diet, and rats fed the high-fat diet were injected with streptozotocin intraperitoneally to generate a model of T2DM. Cataract formation and corneal endothelial cell density were assessed using microscopic analysis. Diabetes-related rat aqueous humor alterations were assessed using metabolomics screening. Transmission electron microscopy was used to assess qualitative ultrastructural changes ciliary process microvessels at the site of aqueous formation in the eyes of diabetic rats and humans. Eyes from the diabetic rats demonstrated cataracts, lower corneal endothelial cell densities, altered aqueous metabolites, and ciliary body ultrastructural changes, including vascular endothelial cell activation, pericyte degeneration, perivascular edema, and basement membrane reduplication. These findings recapitulated diabetic changes in human eyes. These results support the use of this model for studying ocular manifestations of T2DM and support a hypothesis postulating blood-aqueous barrier breakdown and vascular leakage at the ciliary body as a mechanism for diabetic anterior segment pathology.

Assessing quantitatively the state of the blood-aqueous barrier by laser flare photometry: a review

This review discusses the experience in applying laser flare photometry, a non-invasive technique, in ophthalmology, to assess quantitatively the state of the blood-aqueous barrier (BAB) in patients with certain ocular and systemic disorders. The method allows reliable detection of such biomarkers of the state of the BAB as the intensity of the scattered light (flare) and number of cells in the aqueous of the anterior chamber, sometimes even at the subclinical level, which significantly improves the capability for early diagnosis and objective treatment monitoring.

Understanding the Pharmacodynamics of Kriyakalpa

Pharmacodynamics is the study of a drug’s molecular, biochemical, and physiologic effects. In short, it is all about how a drug affects an organism. There are some important factors that play an important role in the absorption of drugs in the body, like the route of drug administration, solubility and bioavailability, physical state of the drug and molecular weight, Time of absorption, and Vascularity of the absorbing surface. In Ayurveda, the local treatment procedures of Netra are explained in the name of Netra Kriya Kalpa (Su. U. 18/2). The word kriya means therapeutic action, and kalpana means specific formulations. Kriya Kalpa is a Bahirparimarjana Chikitsa and has several advantages over oral administration. They are noninvasive and cost-effective. No biodegradation of Drugs, Effective against blood aqueous and blood-retinal barriers, Comparatively, less dose is required, and it can be used as a preventive as well as a curative. Overall, we can say that Kriyakalp Procedures have several advantages as compared to oral administration.

A Case of Intraocular Pressure Rise with Iridocyclitis after Photorefractive Keratectomy

Purpose: To report a case of intraocular pressure (IOP) rise with iridocyclitis after photorefractive keratectomy (PRK).Case summary: A 29-year-old woman who had bilateral PRK to correct high myopia developed a glaucoma with iridocyclitis on 99th day after operation. After treatment of oral steroid and steroid eyedrops and anti-glaucoma eyedrops for 13 months, IOP was controlled within normal limit but peripheral anterior synechia and dyscoria was developed and remained. We have been observing the iridocyclitis that relapses intermittently with use of steroid eyedrops and checking the IOP regularly.Conclusions: The case reported iridocyclitis after PRK without any medical or ophthalmic history. This seems to be multifactorial including inflammatory response induced by PRK or alterations in blood-aqueous humor barrier, which remains obscure. Close follow up for IOP and iridocyclitis is recommended after PRK.

Acute uveitis caused by abnormal glucose and lipid metabolism: a case report

PurposeThis report describes a rare case of acute uveitis with severe anterior chamber inflammation due to abnormal glucose and lipid metabolism.Case presentationA 31-year-old male patient complained of redness in the right eye with decreased visual acuity for 3 days. Ocular examination revealed a milky white clouding of the right anterior chamber of the eye. Two clusters of yellowish-white exudates were visible on the surface of the iris in the upper nasal and temporal areas in addition to elevated intraocular pressure. He had a previous diagnosis of type 2 diabetes mellitus (T2DM). Laboratory tests suggested hyperlipidemia and ketoacidosis. After admission, topical glucocorticoids, mydriasis, and intraocular pressure-lowering drugs combined with hypoglycemic and lipid-lowering therapy and fluid replacement therapy were given immediately. After 10 days of treatment, the uveitis and systemic condition of the right eye were effectively controlled and improved.ConclusionAbnormal glucose and lipid metabolism leads to impairment of the blood-aqueous barrier, which causes a severe uveitis response in the anterior chamber. After the use of topical steroids and mydriatic eye drops combined with systemic hypoglycemic and lipid-lowering interventions, the condition was significantly relieved.

The effect of one- and two–rectus muscle strabismus surgery on anterior chamber flare

To investigate the effect of the most commonly performed strabismus surgery procedures on the blood-aqueous barrier using laser flare photometry (LFP). Patients who underwent unilateral or bilateral strabismus surgery between January 2020 and May 2021 were included. Eyes were grouped according to the number of rectus muscles operated: one rectus muscle procedure (recession) with or without inferior oblique anterization (IOA), ipsilateral two rectus muscle procedure (recession and resection) with or without IOA, and unoperated fellow eyes of patients undergoing unilateral surgery. Anterior chamber flare values were measured by LFP for each eye the day before the surgery and day 1, week 1, and month 1 postoperatively. A total of 66 eyes of 33 patients (21 females) were included. There were 29 eyes in the one-muscle group, 22 in the two-muscle group, and 15 in the fellow-eye group. The mean flare values of the two-muscle group were significantly higher than those of the other groups at postoperative day 1 and week 1 (P = 0.001, for both). The mean postoperative day 1, week 1, and month 1 flare values of the two-muscle group were significantly higher than the mean preoperative flare value. There were no significant differences between pre- and postoperative flare values of the one-muscle or fellow-eye groups (P > 0.05, for both). In our study cohort, LFP provided evidence of subclinical changes in the blood-aqueous barrier up to the first month postoperatively in otherwise healthy patients undergoing two-muscle surgery compared with those undergoing one-muscle surgery and unoperated fellow eyes.

Orbital Lesion as the Initial Manifestation of a Neuroendocrine Tumour

Laser flare photometry provides a non-invasive and objective measurement of the Tyndall effect in the anterior chamber. The laser flare value (measured in photon number per millisecond [pc/ms]) thus quantifies the extent of disruption to the blood-aqueous barrier and can be used in clinical applications to monitor uveitis therapy or to measure the postoperative degree of inflammation. Standardised performance must be observed during measurement. Publications of the last 35years on laser flare photometry deal not only with the measurement procedure but also with its use in clinical practice for different ophthalmological pathologies. Likewise, various influencing factors have already been investigated and described that must be considered when measuring and evaluating laser flare values. The focus of this article is the relevance of laser flare photometry in retinal pathologies. In recently published studies, the level of objective tyndallometry in primary rhegmatogenous retinal detachment is shown to depend on lens status, symptom duration, and extent of retinal detachment. The greater is the area of the retina affected, the greater the disruption of the blood-aqueous barrier appears to be. Elevated laser flare values have also been considered as a predictor for the development of proliferative vitreoretinopathy (PVR). However, based on current knowledge, this assumption must be put into perspective. According to current data, objective tyndallometry can be used to monitor the progression of intraocular inflammation and to quantify the blood-aqueous barrier, and the values correlate with the extent and anatomical features, as well as the symptom duration in retinal detachment. Many influencing factors have already been identified. But further evaluation is desirable and needed. It is still unclear whether laser flare values can be used in the future as a predictor for sequelae such as PVR development.

Region-related and layer-specific permeability of the iris vasculature with morphological mechanism: A novel understanding of blood-aqueous barrier

The permeability of iris blood vessels has an important role in maintaining aqueous humor (AH) homeostasis, contributing to variation in iris volume and probably the pathogenesis of angle closure glaucoma. This study investigates the permeability of the iris microvasculature to plasma-derived protein and correspond it with the morphologic characteristics of vascular mural cells (MCs).Twenty-two enucleated porcine eyes were used in this study. 12 eyes were micro-perfused with vehicle alone as control or with FITC-albumin as a marker of protein leakage and histological sections subsequently made to examine for FITC-albumin presence. The other 10 eyes were immunolabeled via micro-perfusion for αSMA and VE-cadherin to investigate their topographic distribution in the porcine iris vasculature, and to cross correspond with the locations of FITC-albumin deposits.Distribution of FITC-signals exhibited a site-dependent pattern and time-dependent change in the iris. Fluorescence was initially detected around capillaries in the superficial and deep layer of the iris microvascular network. The pupillary region and the iris root retained more fluorescent signal than the iridal ciliary region. At low magnification, αSMA labelling displayed a regional variation which was inversely correlated with vascular permeability. At the cellular level, αSMA labeling corresponded with vascular MCs distribution in the iris vascular network.The correspondence between iris microvascular permeability to FITC-albumin and the pattern of αSMA distribution and MCs coverage adds to the understanding of the elements comprising the blood-aqueous barrier with implications for the bio-mechanics of iris volume change.

Iris angiography in ADAMTS10 mutant dogs with open-angle glaucoma (ADAMTS10-OAG).

To evaluate anterior segment angiographic findings in hypertensive ADAMTS10-open-angle glaucoma (ADAMTS10-OAG) eyes as compared to normotensive control eyes. Nine ADAMTS10-OAG beagles and four wild-type control dogs. Anterior segment angiography was performed under general anesthesia following intravenous injection of indocyanine green (ICG; 1 mg/kg) and sodium fluorescein (SF; 20 mg/kg) using a Heidelberg Spectralis® confocal scanning laser ophthalmoscope. Time to onset of iridal angiographic phases and the presence/severity of dye leakage into the iris stromal and/or aqueous humor were recorded. Group findings were compared, and multiple linear regression analysis was performed to identify potential factor associations with disease status. Time to onset of all angiographic phases visualized using ICG was significantly prolonged while time to onset of SF leakage into the aqueous humor was significantly reduced in glaucomatous eyes compared to controls. Only glaucomatous eyes (n=9) demonstrated evidence of SF stromal leakage. Mean intraocular pressure (IOP) and age were significantly higher, while mean cardiac pulse was significantly lower in glaucomatous eyes compared to controls. Blood pressure and ocular perfusion pressure were not significantly different between groups. Multiple linear regression analysis, controlling for age, IOP, and pulse demonstrated glaucoma, was not predictive of the time to onset of any angiographic phase, stromal, or aqueous humor leakage. However, pulse was a significant factor contributing to the severity of aqueous humor leakage. A compromised vascular supply to the anterior segment exists in dogs with ADAMTS10-OAG. These observations warrant further exploration of what role altered perfusion and/or disruption to the blood-aqueous barrier may play.

Anterior segment inflammation and its association with dry eye parameters following myopic SMILE and FS-LASIK

Purpose To evaluate dry eye and anterior segment inflammation after small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK), and investigate their association. Methods This prospective and observational study included 96 eyes from 48 myopic patients. The evaluation was performed at baseline, postoperative day 1, week 1, month 1 and month 3. Outcome measures included anterior chamber flare, bulbar redness (BR), limbal redness (LR), ocular surface disease index (OSDI), tear meniscus height (TMH), the first and average noninvasive breakup time (NIBUT-1, NIBUT-a), fluorescein breakup time (FBUT), corneal fluorescein staining (CFS), and Schirmer I. Generalized estimating equations (GEEs) were applied to explore the correlation between flare and ocular surface parameters. Results Flare increased significantly in both groups at day 1 and week 1 and then returned to baseline at month 1. In both groups, BR decreased on day 1 and then gradually increased towards the baseline. In FS-LASIK, LR was lower than baseline at day 1 and month 3. An increase in OSDI was found in the SMILE group on day 1, and in the FS-LASIK group at day 1 to month 1. NIBUT-1 and NIBUT-a decreased significantly on day 1 in both groups. At month 3, NIBUT-a did not return to baseline in FS-LASIK. CFS increased significantly at week 1 in both groups. All parameters were comparable between SMILE and FS-LASIK except for OSDI and NIBUT-a. Time and spherical equivalent showed a correlation with flare. Conclusions Both SMILE and FS-LASIK induced elevated anterior chamber flare and dry eye. However, flare might not be considered a factor determining perioperative dry eye. Key Messages Dry eye disease is common after corneal refractive surgery. Signs and symptoms of dry eye disease persist longer after FS-LASIK compared with SMILE. Both FS-LASIK and SMILE transiently disrupted blood-aqueous barrier integrity, leading to anterior segment inflammation. Anterior chamber flare might not be considered a factor explaining perioperative dry eye, other biomarkers remain for future exploration.

Oral 5-aminolevulinic acid combined with sodium ferrous citrate prevents blood-aqueous barrier breakdown after anterior chamber paracentesis in healthy beagle dogs.

This study investigated the preventive effect of 5-aminolevulinic acid combined with sodium ferrous citrate (5-ALA/SFC) on blood-aqueous barrier (BAB) breakdown induced after anterior chamber paracentesis (ACP) in beagles. 5-ALA/SFC (1/0.64 mg/kg or 3/1.92 mg/kg) or carprofen (4.0 mg/kg) was orally administered daily for 7 days prior to ACP. Then, a sample of the aqueous humor (AH) was collected from one eye via ACP (first sample) and again 60 min later (second sample). The protein and prostaglandin E2 (PGE2) concentrations in both samples were measured. Compared with the control group, high-dose 5-ALA/SFC and carprofen significantly reduced the AH protein and PGE2 concentrations in the second sample. Our findings suggest that 5-ALA/SFC suppresses BAB breakdown in dogs.

HLA-B27 positive anterior uveitis : Clinical aspects, diagnostics, interdisciplinary management and treatment

Acute anterior uveitis (AAU) associated with human leukocyte antigen (HLA) B27 is the most common form of noninfectious intraocular inflammation and is considered to be aseparate clinical entity. Young adults between the ages of20 and40 years are predominantly affected. The HLA-B27 positive AAU typically presents as aunilateral, fulminant disruption of the blood-aqueous humor barrier, which is accompanied by pronounced cellular infiltration and fibrinous exudation. Other characteristics are reduced intraocular pressure and ahigh tendency to relapse, which can also involve the partner eye. Patients with HLA-B27 positive AAU share ahigh risk for other genetically associated diseases, especially spondylarthritis, chronic inflammatory bowel diseases and psoriasis. As up to 40% of those affected have asystemic disease that has not yet been diagnosed, the ophthalmologist is of major importance for early detection.

Evaluation of Aqueous Flare in Graves' Ophthalmopathy and its Relationship with Thyroid Hormones, Antibodies, and Clinical Activity Score.

The aim of this study was to assess intraocular inflammation in patients with active and inactive Graves' ophthalmopathy (GO) using an aqueous laser flash meter and to assess its relationship with thyroid hormones, antibodies, and clinical activity score (CAS). Forty patients (29 females and 11 males) were included in the study. The patients were divided into two groups according to CAS; patients with CAS <3 (inactive) were included in Group 1 and patients with CAS ≥3 (active) were included in Group 2. The laser flare meter was used to measure the flare of aqueous humor. Each patient's ocular findings, thyroid hormone, and antibody levels were also recorded. The mean age of patients was 46.88±11.79 years in Group 1 and 44.50±12.59 years in Group 2 (p=0.555). The mean CAS was 0.88±0.65 in Group 1 and 3.57±0.85 in Group 2 (p<0.001). The mean aqueous flare was 6.5±2.2 ph/ms in Group 1 and 7.0±6.4 ph/ms in Group 2 (p=0.73). Hertel exophthalmometry, intraocular pressure (IOP), antithyroglobulin antibody, and thyroid stimulating hormone receptor antibody (TRAb) levels were similar in both groups (each p>0.05). There was no correlation between aqueous flare value and CAS, Hertel exophthalmometry, IOP, thyroid hormone, and antibody levels (each p>0.05). There was a significant correlation between CAS and antibody levels (each p<0.05). Flare values that are not much above the normal range may be an indication that intraocular inflammation is not elevated in GO patients. This suggests that the damage to the blood-aqueous barrier in these patients is not severe enough to increase intraocular inflammation.

Factors influencing aqueous flare after cataract surgery and its evaluation with laser flare photometry.

Despite the refinement of modern cataract surgery, postoperative inflammation still constitutes a substantial amount of visual morbidity worldwide. A surrogate for intraocular inflammation and blood-aqueous barrier breakdown can be objectively quantified by Laser flare photometry (LFP). This review outlines the utility of LFP in assessing the assessment of post-cataract surgery inflammation. It highlights the impact of preoperative pathological states such as uveitis and diabetes, intraoperative techniques, including efficient phacoemulsification and direct comparisons between postoperative anti-inflammatory regimes. There is a large interobserver variation in the subjective flare measurement after cataract surgery and the continued use of LFP amongst other objective, noninvasive measurements of intraocular inflammation, particularly in the further development of cataract surgery, is recommended.

Study of the Permeability of Blood-Aqueous Barrier with Tetracycline Group Drugs in Normal and Pathological Conditions

Study of the Permeability of Blood-Aqueous Barrier with Tetracycline Group Drugs in Normal and Pathological Conditions

Commentary: Treatment of postoperative cystoid macular edema in vitrectomized eyes: An enigma.

Post-operative cystoid macular edema (PCME) is a sight-threatening complication that could affect visual recovery following a successful ocular surgery. Irvine–Gass syndrome, that is, PCME following cataract surgery has extensively been studied. The incidence of clinical CME following phacoemulsification ranges from 0.2% to 2.35%.[1] The incidence of PCME following vitrectomy for vitreous floaters, rhegmatogenous retinal detachment (RRD), and the epiretinal membrane (ERM) has been found to be around 5%, 10–25%, and 13–47%, respectively.[1-4] Although the exact pathophysiology of PCME remains debatable, the most probable cause seems to be subclinical low-grade inflammation. Studies have shown that the levels of cytokines and prostaglandins are elevated in such eyes, leading to blood–aqueous barrier breakdown and consequent fluid accumulation.[1-4] Pole et al.[2] described the optical coherence tomography (OCT) characteristics of PCME after RRD surgery. These included fovea-involving diffuse CME, which involved all four macular quadrants and cysts in the inner nuclear and outer plexiform layers. In untreated eyes, the cysts may coalesce into larger irregular, polygonal-shaped cavities. CME may resolve spontaneously but cause disorganization and atrophy of the retinal layers. Several risk factors for the development of PCME following vitrectomy have been identified. Risk factors following RRD surgery include old age, cataract surgery, macula-off RRD, longer duration, pre-existing proliferative vitreoretinopathy changes (C or higher), intra-operative retinectomy, and multiple surgeries.[12] Risk factors following ERM removal surgery include old age, cataract surgery, stage 4 ERM, and the presence of pre-existing intraretinal cysts.[34] The post-operative tamponading agent did not influence the development of PCME in either pathology.[1-4] To date, there has been no consensus on the treatment for PCME. Its management is often complex due to its recurring nature. The various available treatment options include topical steroid and non-steroidal anti-inflammatory drug (NSAID) drops; intravitreal anti-vascular endothelial growth factor (VEGF) and triamcinolone acetonide (TA) injections; intravitreal dexamethasone and fluocinolone implants; suprachoroidal triamcinolone injection; and posterior subtenon and trans-tenon retrobulbar triamcinolone injection. The efficacy of topical treatment in previously vitrectomized eyes is usually limited.[12] Similarly, anti-VEGF injections also tend to be less effective in vitrectomized eyes due to faster clearance and reduced half-life.[12] Intravitreal triamcinolone acetonide (IVTA) injection has been found to be better than anti-VEGF injections in improving macular thickness and visual acuity.[2] However, the mean elimination half-life in vitrectomized eyes is merely 3.2 days compared to 18.6 days in non-vitrectomized eyes.[5] On the contrary, the vitreoretinal pharmacokinetic profiles of dexamethasone and fluocinolone implants in vitrectomized eyes are similar to that in non-vitrectomized eyes. Intravitreal dexamethasone implant has been found to be an effective treatment option for eyes with PCME following vitrectomy for RRD and even endophthalmitis.[67] Eyes that underwent vitrectomy for ERM compared to RRD, presence of subretinal fluid, intact outer retinal layers, and worse baseline best-corrected visual acuity (BCVA) have higher chances of visual improvement. Owing to the recurrent nature of the disease, multiple injections are often needed.[6] Intravitreal fluocinolone acetonide implant has been shown to achieve persistent functional and anatomical improvement with long recurrence-free periods. Miguel–Escuder et al.[8] suggested that it could be considered as a therapeutical option in eyes with refractory PCME following vitrectomy. Suprachoroidal TA injection with the help of custom-made needles is another treatment option. Due to its unique position, the suprachoroidal space serves as a drug reservoir with slow drug washout and better absorption. Animal model-based pharmacokinetic studies have shown that a 12-fold higher drug concentration can be achieved in the retina along with reduced entry drug in the anterior chamber, thus reducing the risk of intraocular pressure rise and cataract formation.[9] Trans-Tenon’s retrobulbar TA infusion has also been used successfully for the management of refractory diabetic macular edema (DME) in vitrectomized eyes. The described technique included making an incision in the conjunctiva and the Tenon’s capsule in the inferotemporal quadrant followed by infusion of 40 mg triamcinolone acetonide with a 25-gauge curved blunt cannula into sub-Tenon’s space under topical anesthesia.[10] Posterior subtenon triamcinolone (PST) injections have classically been used for the management of intermediate uveitis. It has been shown to provide a sustained high level of TA in the vitreous cavity level along with low systemic TA levels that cannot alter the systemic cortisol levels.[11] We congratulate the authors for their manuscript evaluating the efficacy and safety of PST for the treatment of chronic PCME in vitrectomized eyes.[12] However, prospective randomized studies with a larger sample size are required to compare the efficacy with other treatment modalities. Because simultaneous complicated cataract surgery is itself a risk factor for the development of PCME, eyes with nucleus drop should be excluded. Additionally, the management of a raised intraocular pressure in the steroid responder eyes may be challenging, because the depot of TA in the posterior subtenon location is difficult to remove completely.