Subconjunctival Spaces Research Articles

Bleb-related Porcine Lymphatic Outflow is Greater from Subconjunctival compared to Subtenon Blebs.

Understanding the mechanism of fluid outflow by comparing the subconjunctival and subtenon spaces can lead to improved ocular therapeutics. The purpose of the current study is to evaluate subconjunctival vs subtenon lymphatic outflow by creating tracer-filled blebs in each location. Porcine (n = 20) eyes received subconjunctival or subtenon injection(s) of fixable and fluorescent dextrans. Blebs were angiographically imaged using a Heidelberg Spectralis ([Heidelberg Retina Angiograph] HRA + OCT; Heidelberg Engineering) and bleb-related lymphatic outflow pathways were counted. Optical coherence tomography (OCT) imaging of these pathways was used to assess structural lumens and the presence of valve-like structures. Furthermore, a comparison between tracer injection locations (superior/inferior/temporal/nasal) was made. Histologic analyses for subconjunctival and subtenon outflow pathways were performed, to confirm tracer co-localization with molecular lymphatic markers. Subconjunctival blebs demonstrated a greater number of lymphatic outflow pathways compared to subtenon blebs in every quadrant [superior: 6.10 ± 1.18 (subconjunctival) vs 0.50 ± 0.27 (subtenon); temporal: 2.30 ± 0.40 vs 0.10 ± 0.10; nasal: 5.30 ± 0.60 vs 0.30 ± 0.21; inferior: 6.00 ±1.29 vs 0.1 ± 0.1; all comparisons p < 0.001]. For subconjunctival blebs, the temporal quadrant showed fewer lymphatic outflow pathways compared to the nasal side (p = 0.005). Subconjunctival blebs accessed greater lymphatic outflow compared to subtenon blebs. Furthermore, regional differences existed, with fewer lymphatic vessels temporal than at the other locations. Aqueous humor drainage after glaucoma surgery is incompletely understood. The present manuscript adds to our understanding of how lymphatics might influence filtration bleb function. Lee JY, Strohmaier CA, Akiyama G, et al. Bleb-related Porcine Lymphatic Outflow Is Greater from Subconjunctival compared to Subtenon Blebs. J Curr Glaucoma Pract 2022;16(3):144-151.

Bleb morphology using optical coherence tomography : After primary implantation of XEN gel stent and open conjunctival revision

The implantation of a XEN gel stent is an innovative method for filtration surgery using an ab interno approach. The morphological evaluation of the resulting bleb is decisive for surgical success. Bleb revision is frequently needed after XEN implantation and might affect the bleb morphology. Aim of this study was to examine bleb morphology using anterior segment OCT (AS-OCT) and analyze the morphological differences of blebs after primary XEN implantation and after bleb revision. Included were eyes that underwent XEN implantation (Pr-X) or bleb revision after XEN (Re‑X group). An AS-OCT of blebs was performed and images were classified using a novel classification system (the Jenaer bleb grading system, JBGS). Frequency of different tomographic patterns (M) and their correlation with intraocular pressure (IOP) were analyzed. A total of 69eyes (40in the Pr‑X and 29in the Re‑X groups) were included. At the conjunctival level, the most commonM in both groups was subconjunctival spaces (M-C2) followed by intraconjunctival cysts (C1) and no conjunctival changes (C0). No differences of frequencies between the two groups or of IOP between the three Ms were seen. At the tenon level, the most commonly seen Ms in the Pr‑X group were hyporeflective and cavernous changes (M-T2, T3) followed by no changes (M0) and hyperflective changes (T1). In the Re‑X group, the M‑T1 and T2 were most commonly seen followed by T3 and T0. The M‑T2 and T3 in the Pr‑X group and the M‑T1 and T2 in the Re‑X group correlated with lower IOP. An episcleral lake (M-ES1) was seen significantly less frequently in the Pr‑X group compared with Re‑X group where it correlated with lower IOP CONCLUSION: The hyperreflective changes at the tenon level and the presence of an episcleral lake were seen more frequently following bleb revision compared with primary XEN implantation and correlated with lower IOP. The interpretation of bleb morphology using AS-OCT should only be done considering the surgical approach used.

Novel Bleb Classification Following Ab Interno Implantation of Gel-Stent Using Anterior Segment Optical Coherence Tomography.

A novel qualitative tomographical classification for bleb after implantation of XEN-Gel-Stent using ab interno approach is presented. Association of anatomic patterns to intraocular pressure (IOP) and success rates (SR) illustrates that anterior segment optical coherence tomography can be useful tool in clinical guidance. To present a novel classification of bleb resulting from ab interno implantation of XEN-Gel-Stent and report association of tomographical patterns with IOP and SR. A cross-sectional 1-armed study of patients receiving XEN-Gel-Stent. Tomographical changes in the bleb area were studied using swept-source optical coherence tomography in an early (d 29-90 postsurgery) and late (starting from d 91 postsurgery) phase. Frequency of patterns and their association with IOP and SR (defined as IOP<18mmHg without medications) were studied. One hundred eleven examinations of 49 blebs (49 patients) were included. Three tomographical patterns at conjunctival, 4 at tenons capsule, and 2 at episcleral level were characterized. Most frequent conjunctival pattern was subconjunctival spaces (56.3% and 53.2% in the early and late phase, respectively) and associated with lower IOP (13.0±6.0mmHg) and higher SR (89%) but only in the early phase compared with other conjunctival patterns ( P <0.05). At tenons capsule level, the hyporeflective pattern was most frequent (50% and 51.9% in early and late phase) followed by the cavernous pattern. Both patterns associated with lower IOP and higher SR compared with hyper-reflective or loss of tenon changes ( P <0.005). Most blebs showed no episcleral lake (87.5% and 89.9% in early and late phase). No difference of IOP and SR was noted compared with those showing an episcleral lake. A practical and clinically relevant novel classification system is proposed to tomographically describe and classify blebs after implantation of XEN-Gel-Stent. Certain patterns were associated with lower IOP and higher SR.

Targeting Ocular Drug Delivery: An Examination of Local Anatomy and Current Approaches.

Ocular drug delivery remains the focus of much modern research. Primary routes of administration include the surface, the intravitreal space, the subretinal space, and the subconjunctival space, each with its own series of unique challenges, limitations, and advantages. Each of these approaches requires careful consideration of the local anatomy, physical barriers, and key cells as well as the interface between the anatomy and the drug or drug system being delivered. While least invasive, the topical route poses a challenge with the many physical barriers that prevent drug penetration into the eye; while injection into the intravitreal, subretinal, and subconjunctival spaces are direct and targeted but limited due to the many internal clearance mechanisms and potential for damage to the eye. Polymeric-based, sustained-release drug delivery systems have been identified as a potential solution to many of these challenges; however, the design and successful implementation of a sustained-release system that is well-tolerated, bioactive, biocompatible, and degradable remains, in many cases, only in the early stages. The drugs and biomaterials in question also require special attention as small chemical changes could result in vastly different outcomes. This paper explores the anatomy and key cells of these four primary drug delivery routes as well as the interface between drug and drug delivery systems and the anatomy, reviewing the recent developments and current state of research in each area. Finally, this paper also examines the frequently used drugs and biomaterials found in ocular drug delivery and summarizes the primary interactions observed.

Assessing the Status of Filtering Blebs at 5 Year Post- Trabeculectomy.

BACKGROUND:Glaucoma is a common cause of blindness in the world as well as in Vietnam. It is treated by many different methods but trabeculectomy is still the most popular and highly effective surgical method to treat this condition.AIM:To analyze the status of 5 years filtering blebs following trabeculectomy and to explore multiple factors associated with filtering blebs.METHODS:This is a retrospective, cross-sectional descriptive study. Eyes had been performed trabeculectomy for 5 years were included in these results. The filtering blebs were assessed using slit lamp and OCT. the OCT captured bleb area to evaluate fluid subconjunctival spaces, thickness and height of bleb and to evaluate the related factorsRESULTS:A group of 106 primary glaucoma eyes of 97 patients (88 patients with 1 eye, 9 patients 2 eyes) had been performed trabeculectomy for 5 years were taken OCT anterior image. The proportion of female patients is 1.5 times that of male patients. IOP was controlled with or without topical medication in all eyes. The filtering bleb had a high echo reflection, which accounted for 42.5%, the average echo reflection was 38.6%, the low echo reflection response of 18.9%. 66% of the eyes had the aqueous space under the conjunctiva, 65.1% have the aqueous space under sclera flap, the average height of the bleb on OCT was 0.4 mm ± 0.3 mm. Young patients often have a higher rate of bleb fibrosis and loss of function than older patientsCONCLUSION:OCT is capable of assessing the function of bleb. After 5 years of trabeculectomy, on the OCT image, most cases of blebs are maintaining drainage function.

EphrinB2–EphB4 Signals Regulate Formation and Maintenance of Funnel-Shaped Valves in Corneal Lymphatic Capillaries

To elucidate the role of signals mediated by EphB4 receptor tyrosine kinase and its transmembrane ephrinB2 ligand in corneal lymphatic capillaries. To detect expression of ephrinB2 and EphB4 in mouse corneas, immunohistochemistry of flat-mount corneas from 6- to 10-week-old wild-type, Efnb2-lacZ, and Ephb4-lacZ mice on a C57BL/6 background was performed. To induce formation of new blood vessels and lymphatic vessels, mouse corneal epithelia were swabbed with 0.1 M sodium hydroxide. To antagonize endogenous receptor-ligand interactions in corneal lymphatic vessels, recombinant EphB4/Fc proteins were injected into the subconjunctival spaces. To visualize the corneal lymphatic flow, FITC-dextran was injected subconjunctivally. In lymphatic capillaries of adult mouse corneas, EphB4 was intensively expressed in lymphatic endothelial cells (LECs) of funnel-shaped valves, which were segregated from ephrinB2-expressing LECs. The number of corneal lymphatic valves was significantly decreased by Efnb2 haploinsufficiency, and subconjunctival EphB4/Fc injections resulted in the deformation of preexisting valves of corneal lymphatic capillaries. In alkali-burn corneas, ephrinB2 and EphB4 were highly expressed in LECs of valve-forming areas. Subconjunctival EphB4/Fc injections perturbed the morphologic maturation of new lymphatic valves, leading to reflux of FITC-dextran to peripheral lymphatic branches. The results demonstrate a pivotal role of ephrinB2-EphB4 signals in the formation and maintenance of funnel-shaped valves in corneal lymphatic capillaries, and further suggest the potential of ephrinB2-EphB4 signals as a target to therapeutically manipulate corneal lymphangiogenesis.

Noncontact In Vivo Scanning Laser Microscopy of Filtering Blebs

To evaluate the ability of a noncontact, prototype scanning laser confocal microscope to image microstructural features of filtering blebs in vivo and to correlate these with the clinical features. Thirty-one blebs of 24 patients underwent noncontact in vivo confocal microscopy using the Rostock Cornea Module of the Heidelberg Retina Tomograph II (50x noncontact Nikon lens, 1-2 mum resolution, field of view: 500x500 mum). Blebs were clinically classified as successful (low, diffuse, microcystic, and hypovascular) (n=22, mean intraocular pressure<20 mm Hg without hypotensive medications) or failed (flat, cicatrized, and nonfiltering) (n=9, mean intraocular pressure>20 mmHg with or without hypotensive medications). Multiple transverse images were taken over the scleral flap at 1 to 2 mm from the limbus. Images were evaluated by 2 observers masked to clinical appearance and function of the bleb. Transverse images of the successful blebs showed epithelial microcysts (50 to 100 microm) and small-sized to medium-sized (100 to 150 microm) subconjunctival cystic spaces with scattered loose collagen-like networks around the scleral flap. Failed blebs showed diffuse hyperreflective dense stroma, increased and tortuous vascularization, and no cystic spaces. The microscopic findings of all blebs were consistent with previous reports of contact in vivo confocal microscopy. Noncontact in vivo confocal microscopy of filtering blebs correlated with the clinical morphology. This noncontact approach provides information about bleb morphology without the risk of bleb microinjury, leak, or infection. Further study and optimization for imaging surface tissues are needed to improve our understanding of bleb maturation and wound healing.

Ultrasound Biomicroscopy and Optical Coherence Tomography Imaging of Filtering Blebs after Deep Sclerectomy with New Collagen Implant

To identify the clinical and anatomic characteristics of filtering blebs after glaucoma surgery with a new biodegradable collagen implant, Ologen, using ultrasound biomicroscopy (UBM) and Visante anterior segment optical coherence tomography (OCT). The authors conducted a prospective interventional case series in 15 eyes with openangleglaucoma. The authors performed limbal-based deep sclerectomy with Ologen implantation in the scleral bed. UBM, Visante anterior segment OCT, and a complete ophthalmic examination were performed at each follow-up visit, at 1 day, and 1, 4, and 12 weeks postoperatively. Intraocular pressure (IOP) was significantly reduced (p<0.001) from a mean preoperative value of 24.2-/+6.8 mmHg (n=2.82 glaucoma medications) to a mean postoperative value of 8.1-/+1.2 (n=0), 8.5-/+1.3 (n=0), 11.7-/+3.2 (n=0), and 14.2-/+3.9 mmHg (n=0.33) at 1 day, and 1, 4, and 12 weeks, respectively. Lower IOP correlated with bleb height and low trabeculocorneal membrane thickness (r=0.79, p<0.01, r=0.91, p<0.001) based on UBM examination. Lower IOP correlated with thin bleb wall, large subconjunctival fluid spaces, and low bleb tissue reflectivity (r=0.81, p<0.01, p<0.001, and p<0.001) based on OCT examination. No postoperative complications were reported. UBM and OCT examinations are useful methods to evaluate outflow mechanisms after glaucoma surgery. Deep sclerectomy with Ologen implantation seems to be an effective and well-tolerated method to reduce IOP.

Control of filtering bleb scarring trough tissue bioengineering

Abstract Purpose To evaluate the effects on intraocular pressure (IOP) reduction and bleb morphology of a new biodegradable collagen implant iGen TM, a porous matrix reducing scar formation after glaucoma surgery. Methods We conducted a prospective interventional case series in 18 eyes of 18 patients with uncontrolled primary open‐angle glaucoma. We performed limbal‐based deep‐sclerectomy with implantion of the device in the scleral bed. We performed a complete ophtalmic examination, ultrasound biomicroscopy (UBM) and Visante anterior segment Optical Coherence Tomography (OCT) at each follow up visit, scheduled 1 day, 1 week, 4 and 12 weeks post‐operatively. Results Postoperative IOP decreased significantly (p &lt; 0.001) from a preoperative mean value of 25.1 ± 5.9 mm Hg (n = 2.73 glaucoma medications) to a postoperative mean value of 8.0 ± 1.1 (n = 0), 8.3 ± 1.2 (n = 0), 11.5 ± 3.0 (n = 0) and 14.1 ± 3.7 mm Hg (n = 0.28) at 1 day, 1week, 4 and 12 weeks respectively. Characteristic imaging parameters of successful bleb were frequently observed (14/18 patients): high and hypoechoic bleb with UBM; thin and hyporeflective bleb wall, multiple subconjunctival fluid spaces and hyporeflective deep bleb tissue with OCT. Bleb height and trabeculocorneal membrane thickness are correlated with low IOP (r = 0.91 p &lt; 0.01, r = 0.90 p &lt; 0.001) with UBM examination. Thin bleb wall, large subconjunctival fluid spaces and low reflectivity of bleb tissue are associated with lower IOP (r = 0.81 p &lt; 0.01, p &lt; 0.001 and p &lt; 0.001) with OCT examination. No post‐operative complications were reported. Conclusion In our series, deep‐sclerectomy with iGen TM implantation seems to be an effective and well‐tolerated method to lower IOP and avoid conjunctival scarring.

Traumatic transconjunctival orbital emphysema.

Orbital emphysema can be produced by trans-conjunctival migration of air from a high pressure airgun. In an industrial accident an 8 mm conjunctival laceration was produced in the superior fornix which acted as a portal of entry for air into the subconjunctival, subcutaneous, and retrobulbar spaces. Computed tomography revealed no evidence of orbital fracture and showed that traumatic orbital emphysema occurred without a broken orbital bone.

Experimental immunogenic orbital inflammation.

Acute orbital inflammation has been induced by injecting bovine serum albumin into the retrobulbar space of rabbits that have been systemically immunized to the same antigen. The principal clinical signs of proptosis, conjunctival chemosis, and lid swelling appear within three hours after injection and are most severe after 24 hours. Signs of anterior chamber reaction, cells and flare, appear as early as two hours after injection. Histologic changes consist of a polymorphonuclear (PMN) cell infiltration throughout the orbit including muscle, optic nerve sheaths, perivascular and subconjunctival spaces. The optic nerve itself is spared. The choroid and the outer layer of the retina show changes as early as six hours after injection. Maximum reaction of massive PMN cell infiltration occurs by 24 hours after injection. It is proposed that the widespread inflammation is due to direct diffusion of antigen throughout the orbit and along the vessels into the choroid.

The Use of Absorbable Gelatin Film (Gelfilm) in Glaucoma Filtration Surgery

The success of fistulizing operations for the relief of hypertension in glaucoma depends in large measure upon the creation of a filtering area in the subconjunctival spaces. While it can be argued that the filtration factor is not the entire answer to the problem, as maintained, for instance, in the neurohumoral theory, it is certainly one of the most potent reasons for the prevalence of these procedures in this country. In order to secure permanent filtration from the anterior chamber to the immediate subconjunctival spaces, many substances working upon the principle of the seton operation have been employed, such as threads, gold drains, and horsehair, and quite recently Qadeer 1 has employed acrylic plates made of the same material as that used for the Ridley implants. Most of these substances have been discarded after trial and failure because they were irritating to the eye and, as a result, frequently increased

Role of cortisone in glaucoma surgery; experimental results.

THE GOAL of all types of surgery employing an iris-inclusion or a trephine technique is to establish a permanent patent fistula from the anterior chamber to the subconjunctival spaces. However, the fundamental drawback of all such operations has been the too frequent failure of these artificially created channels to remain patent; in too many cases the pathways so created are obliterated when the normal process of wound healing occurs. Any process or drug which could delay fibrous tissue formation would be a boon indeed to the ophthalmic surgeon practicing glaucoma surgery. In 1950 Ragan and associates,1while working on rabbits, demonstrated that cortisone had the ability to delay wound healing. Spain and associates,2employing mice, came to the same conclusion, stating: Unquestionably, cortisone inhibits the formation of granulation tissue.... The effect is rapid and of short duration. Spain and his co-workers also found that cortisone was effective in

Experimental study on the efficiency of different substances in retarding the absorption of penicillin introduced into the subconjunctival spaces.

Experimental study on the efficiency of different substances in retarding the absorption of penicillin introduced into the subconjunctival spaces.

CYCLODIALYSIS WITH INSERTION OF A METAL IMPLANT IN THE TREATMENT OF GLAUCOMA

Since Heine devised cyclodialysis (1905) the operation has been tried extensively by many surgeons. It has been called an internal fistulization in the belief that it creates a direct internal channel between the anterior chamber and the suprachoroidal space. Its action is opposed to external fistulization, in which the anterior chamber is made to communicate with the subconjunctival spaces outside of the eye by a trephine or a Lagrange operation. Cyclodialysis is preferred by some surgeons because it is harmless and free from the dangers of secondary infection. Unfortunately its effects in relieving hypertension are almost always temporary. A permanent result is obtained in only about 20 per cent of the cases. The great number of failures has been ascribed to an earlier and complete cicatrization of the detached scleral insertion of the ciliary body to the scleral spur, which reattaches itself, blocking the aperture between the anterior chamber and