Comparison of complications after Ahmed versus Baerveldt implant in glaucoma patients: one year follow-up

AIM: To compare surgical results of the Ahmed and Baerveldt implant procedures in glaucoma patients at 1y follow-up at Jakarta Eye Center (JEC) Eye Hospitals. METHODS: This cohort retrospective study was conducted on glaucoma patients aged ≥18y who had undergone Ahmed and Baerveldt implant surgery. Intraocular pressure (IOP), visual acuity, glaucoma medication, success rate, early and late postoperative complications, and the number of resurgeries were analyzed. RESULTS: A total of 351 eyes in the Ahmed group and 94 eyes in the Baerveldt group were included in this study. At 1y follow-up, the mean IOP was found to be significantly lower in the Baerveldt group (13±4.47 mm Hg) compared to the Ahmed group (15.02±5.73 mm Hg; P=0.025). Glaucoma medication was required in both the Ahmed and Baerveldt groups (58.92% vs 71.67%). Comparable success rate was found in both groups. The Ahmed group revealed a complete and qualified success of 86.82%, and failure of 13.17%. Similarly, the Baerveldt group showed complete and qualified success in 87.75% and failure in 12.25% cases. In the Ahmed group, 11.97% early complications, 26.06% late complications and 9.97% resurgeries were observed. In comparison, in the Baerveldt group, 23.40% early complications, 30.95% late complications and 11.70% resurgeries were observed. CONCLUSION: Both groups of glaucoma implants show significant IOP reduction, however, the Baerveldt implant group demonstrates greater IOP reduction with more failure rates and complications than the Ahmed implant group.     

兔玻璃体内注射聚N-异丙基丙烯酰胺-聚氧化乙烯纳米粒的眼内毒理学效应

目的:评估玻璃体腔内注射新型缓释给药载体聚N-异丙基丙烯酰胺-聚氧化乙烯(PNIPAAm-PEO)纳米粒的眼内毒理学效应。方法:玻璃体腔注射不同浓度(1mg/0.1mL,2mg/0.1mL,3mg/0.1mL,4mg/0.1mL)的PNIPAAm-PEO纳米稀释液后于不同时间点行裂隙灯、检眼镜、视网膜电图以及组织病理学检测。对照组注射0.1mL无菌生理盐水。将所用不同浓度稀释液局部点眼,观察局部组织的刺激反应。结果:兔眼角结膜对检测浓度范围内的PNIPAAm-PEO有良好耐受性,眼部无刺激症状。玻璃体腔内注射1mg和2mg组未见明显视网膜毒性反应。3mg组眼底检查无异常,ERG-b波1~3d下降幅度>30%,第7~14d略有恢复;第14d光镜下视网膜部分感光细胞外节间隙增宽,外丛状层以内结构空泡变性,细胞排列正常;电镜下各层均有较明显的结构改变,广泛的细胞水肿和空泡变性,细胞间隙增宽,感光细胞膜盘结构基本正常。4mg组ERG-b波波幅下降>30%;第1~14d组织病理学观察均有明显视网膜结构破坏,广泛空泡变性,部分感光细胞的盘膜崩解,层状结构紊乱、模糊不清。结论:PNIPAAm-PEO纳米粒的眼部耐受性良好,具有用作眼部给药载体的潜力,但大剂量使用时应注意眼部安全性问题。     

Intraocular pressure elevation after intravitreal or posterior sub-Tenon triamcinolone acetonide injection

BACKGROUND: Despite the benefits of intraocular steroids for the treatment of inflammatory, neovascular, proliferative, and edematous diseases, one of the side effects is raised intraocular pressure (IOP). In this study, we attempted to identify when IOP elevates, peaks, and returns to the preinjection baseline IOP after intravitreal or posterior sub-Tenon administration of triamcinolone acetonide, as well as the factors that might affect IOP. METHODS: Retrospective case review was undertaken of 69 patients (82 eyes), who received either a 4 mg intravitreal (16 eyes) or a 20 mg posterior sub-Tenon (66 eyes) triamcinolone acetonide injection. IOP assessment for each eye was completed at the preinjection baseline and at the first, third, and sixth month of follow-up. RESULTS: The mean IOP of all eyes increased significantly at each follow-up. The mean maximum elevation ratio from the baseline was 4.0 (SD 5.2) mm Hg. An elevation of 5 mm Hg or greater occurred in 28 eyes (34.1%). The maximum elevation correlated significantly with age (p < 0.01). The incidence of an elevation of 5 mm Hg or greater was significantly higher among patients younger than 60 years (p < 0.01) and relatively higher among female patients (p = 0.051). The mean IOP increased significantly at the first month after intravitreal injection but at all follow-up periods after posterior sub-Tenon injection. There was no significant difference in IOP elevation according to disease type, although eyes with diabetic retinopathy tended to be at higher risk of IOP elevation. Two eyes of two female patients, who had received posterior sub-Tenon injections for the treatment of diabetic retinopathy, required glaucoma surgery. INTERPRETATION: The IOP elevation of 5 mm Hg or greater observed in 34.1% of the eyes was consistent with past reports. IOP elevation was associated with patients of less than 60 years of age and with female sex, and it lasted longer after posterior sub-Tenon injection than after intravitreal injection. Careful assessment of IOP during a follow-up period of at least 6 months is paramount, especially in younger female patients after posterior sub-Tenon injection.     

Safety and pharmacokinetics of a preservative-free triamcinolone acetonide formulation for intravitreal administration

PURPOSE: The safety and pharmacokinetics of a triamcinolone acetonide (TA) preservative-free (TA-PF) formulation were investigated after intravitreal administration in rabbits. METHODS: A TA-PF formulation was prepared as a sterile 40-mg/mL or 160-mg/mL suspension in single-use vials by adding TA powder to 0.5% hydroxypropyl methylcellulose in normal saline. TA-PF (4-mg and 16-mg doses) and Kenalog (Bristol-Myers-Squibb, Princeton, NJ) (4-mg dose) were injected into the vitreous of separate groups of rabbits, and drug levels were measured in the vitreous over time with HPLC. Ocular toxicology (clinical examination, serial electroretinography, and histopathologic analysis) was evaluated in a separate group of animals after intravitreal TA-PF injection. RESULTS: The half-lives of the injection amount in the vitreous, 4-mg TA-PF, 16-mg TA-PF, and 4-mg Kenalog, were found to be 24 days, 39 days, and 23 days, respectively. There were no signs of toxicities by clinical examination after TA-PF injection. Serial electroretinograms of rabbits receiving either 4-mg or 16-mg intravitreal TA-PF injections remained normal over time. Histopathologic analysis showed normal ocular tissues in animals receiving either 4-mg or 16-mg intravitreal TA-PF injections. CONCLUSION: The half-life of TA in the vitreous after a 4-mg injection of either TA-PF or Kenalog was comparable. A 16-mg dose of TA-PF produced a long vitreous half-life, and this may be of clinical benefit in patients requiring 6 months of drug exposure in the eye for a chronic disease.     

Peribulbar poloxamer for ocular drug delivery

Purpose: The use of biopolymers in peribulbar injection for controlled drug delivery provides alternative options to eyedrops and intravitreal or surgical methods. Polymerizable biopolymers are especially likely to have a role because of their particular properties. In liquid form, they can be easily injected into the target site and, after polymerization, they provide a prolonged and controlled release of the drug. This study was undertaken to demonstrate the suitability of a thermopolymerizable biopolymer poloxamer (Lutrol F127) for peribulbar injections and controlled drug release. Methods: The toxicity of injected poloxamer compounds was evaluated by visual inspection and histological and immunohistochemical tissue evaluation. The release of marker substances such as 5(6)‐carboxyfluorescein (376 Da) or fluorescein isothiocyanate‐dextran (FITC‐dextran) (4?40 kDa) from poloxamer was used to simulate drug release and penetration into the eye using in vivo fluorometry. Results: According to our clinical and pathological analyses, poloxamer was well tolerated in peribulbar injections and did not cause acute toxicity at the site of injection. The marker compounds were released from the site of injection during the first 24 hours. Conclusions: Although poloxamer appears to be suitable for peribulbar injections, a more prolonged period of dissolution is desirable for clinical purposes.     

Downregulation of endotoxin-induced uveitis by intravitreal injection of vasoactive intestinal Peptide encapsulated in liposomes

PURPOSE: To reestablish the immunosuppressive microenvironment of the eye, disrupted by ocular inflammation during endotoxin-induced uveitis (EIU), by means of intravitreal injection of vasoactive intestinal peptide (VIP) in saline or encapsulated in liposomes, to increase its bioavailability and efficiency. METHODS: EIU was induced in Lewis rats by subcutaneous injection of lipopolysaccharide (LPS). Simultaneously, animals were intravitreally injected with saline, saline/VIP, VIP-loaded liposomes (VIP-Lip), or unloaded liposomes. EIU severity and cellular infiltration were assessed by clinical examination and specific immunostaining. VIP concentration was determined in ocular fluids by ELISA. Ocular expression of inflammatory cytokine and chemokine mRNAs was detected by semiquantitative RT-PCR. Biodistribution of rhodamine-conjugated liposomes (Rh-Lip) was analyzed by immunohistochemistry in eyes and regional cervical lymph nodes (LNs). RESULTS: Twenty-four hours after intravitreal injection of VIP-Lip, VIP concentration in ocular fluids was 15 times higher than after saline/VIP injection. At that time, EIU clinical severity, ocular infiltrating polymorphonuclear leukocytes (PMNs), and, to a lesser extent, ED1(+) macrophages, as well as inflammatory cytokine and chemokine mRNA expression, were significantly reduced in VIP-Lip-injected rats compared with rats injected with saline/VIP, unloaded liposomes, or saline. Rh-Lip was distributed in vitreous, ciliary body, conjunctiva, retina, and sclera. It was internalized by macrophages and PMNs, and VIP colocalized with liposomes at least up to 14 days after injection. In cervical LNs, resident macrophages internalized VIP-Rh-Lip, and some adjacent lymphocytes showed VIP expression. CONCLUSIONS: VIP was efficient at reducing EIU only when formulated in liposomes, which enhanced its immunosuppressive effect and controlled its delivery to all tissues affected by or involved in ocular inflammation.     

Viral Retinitis following Intraocular or Periocular Corticosteroid Administration: A Case Series and Comprehensive Review of the Literature

Abstract

Purpose: To describe viral retinitis following intravitreal and periocular corticosteroid administration.

Methods: Retrospective case series and comprehensive literature review.

Results: We analyzed 5 unreported and 25 previously published cases of viral retinitis following local corticosteroid administration. Causes of retinitis included 23 CMV (76.7%), 5 HSV (16.7%), and 1 each VZV and unspecified (3.3%). Two of 22 tested patients (9.1%) were HIV positive. Twenty-one of 30 (70.0%) cases followed one or more intravitreal injections of triamcinolone acetonide (TA), 4 (13.3%) after one or more posterior sub-Tenon injections of TA, 3 (10.0%) after placement of a 0.59-mg fluocinolone acetonide implant (Retisert), and 1 (3.3%) each after an anterior subconjunctival injection of TA (together with IVTA), an anterior chamber injection, and an anterior sub-Tenon injection. Mean time from most recent corticosteroid administration to development of retinitis was 4.2 months (median 3.8; range 0.25–13.0). Twelve patients (40.0%) had type II diabetes mellitus. Treatments used included systemic antiviral agents (26/30, 86.7%), intravitreal antiviral injections (20/30, 66.7%), and ganciclovir intravitreal implants (4/30, 13.3%).

Conclusions: Viral retinitis may develop or reactivate following intraocular or periocular corticosteroid administration. Average time to development of retinitis was 4 months, and CMV was the most frequently observed agent. Diabetes was a frequent co-morbidity and several patients with uveitis who developed retinitis were also receiving systemic immunosuppressive therapy.     

Posterior juxtascleral injection of anecortave acetate: magnetic resonance and echographic imaging and localization in rabbit eyes

PURPOSE: To confirm juxtascleral delivery of anecortave acetate in rabbit eyes by ocular imaging techniques and to determine drug localization and distribution as a function of time after injection. METHODS: Four female New Zealand white rabbits (weight, 2.5-3.0 kg) received a single juxtascleral posterior sub-Tenon capsule injection of 0.5 mL or 1 mL of 30 mg/mL anecortave acetate. Rabbit eyes were imaged with ultrasonography and magnetic resonance imaging (MRI) before injection, immediately after injection, and at 2 hours, 1 week, and 4 weeks after injection. Rabbit eyes were also imaged with b-mode ultrasonography during the juxtascleral injections. RESULTS: Ultrasonography and MRI demonstrated that juxtascleral posterior sub-Tenon capsule injection of anecortave acetate effectively delivered the drug in direct apposition to the posterior pole of the rabbit eye. The drug remained in the juxtascleral site for at least 5 weeks. The drug was visualized clearly by MRI immediately after injection, decreasing in intensity thereafter. Cannula insertion and the drug delivery process were clearly visualized by real-time ultrasound analysis. Immediately after drug injection, ultrasonography indirectly localized anecortave acetate localization as an echolucent zone posterior to the scleral surface. At the later time points, however, the juxtascleral location of the drug was verified with ultrasonography as a relatively echogenic focus in the same location. CONCLUSIONS: Juxtascleral administration of anecortave acetate via a posterior sub-Tenon capsule approach effectively delivered the drug to the desired position in direct apposition to the globe posteriorly. MRI and ultrasonography both demonstrated that anecortave acetate remained localized to this location for at least 5 weeks after initial injection.     

The treatment of choroidal neovascularisation with intravitreal injections of bevacizumab (Avastin)

BACKGROUND: Although bevacizumab (Avastin) has only been approved for the treatment of colorectal carcinoma, many reports have shown that its intravitreal administration against choroidal neovascularisation (CNV) leads to a stabilisation or even a regression of the pathological neovessels, and thus to a positive evolution of visual acuity. PATIENTS AND METHODS: From April 2006 to July 2007, the CNV of different aetiologies were treated with intravitreal injections of bevacizumab (1.25 mg in 0.05 mL) in 300 patients with an average age of 75, 78 years. Fluorescein angiography and optical coherence tomography were used for the diagnosis and for the checks which were carried out every twelve weeks. The intravitreal injections were performed every six weeks until the macular findings were considered to be dry. The visual acuity was checked using an ETDRS chart. RESULTS: In all the groups considered the visual acuity was stabilised or improved on an average with + 4.44 ETDRS letters after 3.04 injections. During the follow-up six cardiovascular diseases were diagnosed and in one case a patient died. No ocular complications were reported after 1036 injections. CONCLUSIONS: The results clearly show that the intravitreal injections of bevacizumab are effective, safe and cost-effective. However, further randomised studies are needed to confirm the duration of the effect, as well as the good ocular and systemic tolerability of the drug.     

Pharmacokinetics of a long-lasting anti-VEGF fusion protein in rabbit

Conbercept(KH902), a recombinant fusion protein in clinical trial II/III, shows good potential to treat the neovascular age-related macular degeneration (AMD). This investigation evaluated its ocular pharmacokinetics and pharmacodynamic profile in rabbits following intravitreal administration (IVT). Rabbits (n = 120) received single bilateral conbercept IVT administration or single IV administration. Conbercept concentrations in ocular tissues and serum were measured after dosing. VEGF concentration was also measured simultaneously. The results showed that conbercept rapidly distributed from vitreous into targeted tissues and lasted over 81 days. Clearance in ocular tissues was parallel and exhibited a terminal half of 2.5-4.2 days. The drug exposure in the retina was 1/4 to 1/5 of that in vitreous. Serum conbercept concentrations after IVT dosing were low and bioavailability was approximately 44%. And single intravitreal injection induced that ocular VEGF concentration declined over 60 days and serum VEGF concentration decreased for a short time but rebounded to higher level than baseline later. All these indicated conbercept good pharmacokinetic profile in rabbits, with good ocular tropism and systemic tolerance. Combined with the efficacy data from our earlier in vitro and in vivo studies, it should have a promising clinical application for AMD treatment.     

Intravitreal drug delivery by microspheres of biodegradable polymers

We evaluated the efficacy of microspheres of biodegradable polymers as a slow releasing drug delivery system in the vitreous body. Microspheres containing 5-FU were prepared with polymers of poly-(lactic acid) or copolymers of glycolic acid and lactic acid. The release of the drug was studied in vitro. Poly-(lactic acid) microspheres released 5-FU for 7 days. The intravitreal kinetics of the microspheres was studied in rabbits in vivo. The microspheres disappeared from the vitreous cavity of normal eyes by 48 +/- 5 days after injection. Disappearance was accelerated from the vitreous cavity of vitrectomized rabbits (14 +/- 2 days, p less than 10(-6)). No abnormality was found on electroretinographic or histological examinations after microspheres injection. These results suggested that microspheres of biodegradable polymers could be useful as a potential drug delivery system for sustained drug release in the vitreous body.     

Effects of perioperative managements on ocular surface microbiota in intravitreal injection patients

AIM:To investigate the effects of on ocular surface microbiota in patients who received intravitreal injections.METHODS:Samples of ocular surface microbiota were obtained from 41 eyes of 41 patients who visited the Department of Ophthalmology.Patients were separated for three groups.Group A did not receive perioperative managements or intravitreal injection.Group B1 received only once and B2 received more than twice.In operating room,the samples were collected on the ocular surface.Operating taxonomic units(OTUs) clustering and alpha/beta diversity analysis was performed.The microbial 16S rRNA from samples were analyzed using the Hi Seq 2500 platform.RESULTS:Alpha diversity did not differ in each group,and beta diversity differed in the B2 group.Beta diversity showed a significant difference between Group A and B2(P=0.048).With the perioperative managements before intravitreal injection,the composition and relative abundance were altered.Top 10 microbiota on phylum and genus level,and then microbiota notably changed at genus level were listed.Gram-negative bacteria were varied more.Furthermore,Proteus was not found in Groups A and B1,but it was appeared after the patients received perioperative management and intravitreal injections in Group B2.CONCLUSION:With the perioperative managements,the balance of microbiota on the ocular surface is destroyed,and relative composition and abundance of microbiota on the ocular surface is obviously altered.The clinical doctors should pay more attention on the consequence of perioperative managements before intravitreal injection.     

Cytomegalovirus retinitis after fluocinolone acetonide (Retisert) implant

PURPOSE: To report a case of cytomegalovirus (CMV) retinitis after placement of a fluocinolone acetonide (Retisert) implant. DESIGN: Interventional case report. METHODS: Retrospective chart review. RESULTS: A 65-year-old man with a history of Adamantiades-Behcet disease and bilateral recurrent uveitis that was unresponsive to systemic corticosteroid-sparing immunosuppressive therapy developed clinical evidence of CMV retinitis after receiving his second intravitreal Retisert implant in the left eye, while on no systemic immunosuppression. He did not develop CMV retinitis in the right eye despite multiple intraocular and periocular steroid injections. The patient responded well to intravitreal foscarnet followed by placement of an intravitreal ganciclovir implant. CONCLUSIONS: Ophthalmologists should be aware of the potential risk for development of CMV retinitis after local ocular immunosuppressive therapy.     

A study on the toxicity of intravitreal levofloxacin in rabbits

PURPOSE: To investigate the retinal toxicity of different doses of intravitreal injections of levofloxacin in a rabbit model, which is the levorotatory component of ofloxacin and approximately twice as potent as ofloxacin and highly active in vitro against gram-positive and -negative bacteria, and anaerobic bacteria including many ocular pathogens. METHODS: Sixteen albino rabbits were used in this study, and divided four groups. Levofloxacin in doses of 50, 100, 250 and 500 microg was injected into the midvitreous of rabbit's left eyes. The other eye served as a control and received normal saline solution. Indirect ophthalmoscopy, electroretinography (ERG) and light microscopy were used for retinal toxicity of levofloxacin. ERGs were recorded before injection and at 1(st) day, 1(st), 2(nd) and 4(th) weeks. At the end of follow-up period, the rabbits were killed and the eyes were enucleated for histologic evaluation. RESULTS: Intravitreal injections of 50, 100, 250 and 500 microg levofloxacin did not cause any deterioration of the a-wave, b-wave or oscillatory potentials of ERG throughout the follow-up period of 4 weeks. No evidence of retinal toxicity was observed by indirect ophthalmoscopy and light microscopy in any case. CONCLUSIONS: In therapeutic doses of 500 microg or less, intravitreal levofloxacin does not have retinal toxicity in rabbit eyes and this dose was well above the MIC(90) values of ocular pathogens that cause endophthalmitis. If future studies in other species confirm our findings, intravitreal levofloxacin may be a potentially important drug in the treatment and prevention of clinical bacterial endophthalmitis.     

Ocular pharmacokinetic study of a corticosteroid by F MR

Traditional ocular pharmacokinetic studies are invasive and cannot be easily applied to humans in vivo. To acquire in vivo ocular pharmacokinetic data noninvasively, ¹⁹F MR on a 3T clinical scanner was used to follow the real time dynamics of a corticosteroid in the eye. ¹H MR was also performed to locate the site of administration. Triamcinolone acetonide phosphate (TAP) was the model drug, administered by intravitreal and subconjunctival injections. TAP pharmacokinetics were monitored by changes in the ¹⁹F spectrum of the intraocular drug in real time. The elimination half-lives of TAP in the eye after intravitreal and subconjunctival injections were 8 and 0.5 h in vivo and 17 and 6.0 h postmortem, respectively. The half-lives associated with clearance were 14 h for intravitreal injection and 0.5 h for subconjunctival injection.     

Intravitreal toxicology and duration of efficacy of a novel antiviral lipid prodrug of ganciclovir in liposome formulation

PURPOSE: To evaluate the intraocular safety and antiviral treatment efficacy of the sustained lipid prodrug of ganciclovir, 1-O-hexadecylpropanediol-3-phospho-ganciclovir (HDP-P-GCV), as an intravitreal injectable drug system for viral retinitis. METHODS: HDP-P-GCV was synthesized by coupling 1-O-hexadecyl-propanediol-3-phosphate to either free hydroxyl of ganciclovir in pyridine with dicyclohexylcarbodiimide as catalyst. The compound was formulated into liposomes. The antiviral activity was assessed by DNA reduction in vitro, and intraocular safety was assessed by ophthalmoscopy, electrophysiology, and histology after intravitreal injections, with resultant intravitreal concentrations of 0.2, 0.632, 1.12, and 2 mM. The treatment efficacy was evaluated by simultaneous intravitreal injection of HDP-P-GCV and herpes simplex virus type 1 (HSV-1) or by intravitreal injection of HDP-P-GCV at various times before HSV-1 intravitreal inoculation. Retinitis was scored with ophthalmoscopy and compared with controls. RESULTS: In vitro, the IC50 of HDP-P-GCV against HSV-1 and human cytomegalovirus (HCMV) infected cells was 0.02 and 0.6 microM, respectively. In rabbits in vivo, HDP-P-GCV dispersed evenly and maintained a good vitreous clarity at all doses except 2 mM final intravitreal concentration. Although cataracts were observed in some eyes at the higher doses, they were not observed in eyes with 0.2 mM final intravitreal concentration. No other indications of ocular toxicity were observed. Intravitreal injection of HDP-P-GCV with resultant 0.2 mM intravitreal concentration in the HSV-1 retinitis rabbit model demonstrated a complete protection of the retina with the simultaneous treatment strategy and a 4 (P = 0.03) to 6-(P = 0.058) week significant protection of retina with the pretreatment strategies when compared with ganciclovir or blank liposome controls. CONCLUSIONS: In the rabbit model of HSV-1 retinitis HDP-P-GCV acts as a long-lasting intravitreal injectable anti-CMV or anti-HSV compound. This self-assembling liposome system could be applicable for many compounds available for intraocular diseases.     

Tolerability and pharmacokinetics of intravitreal sirolimus

Abstract Purpose: To evaluate the pharmacokinetics (PK) and tolerability of a proprietary sirolimus depot-forming ocular formulation in rabbits and humans after a single intravitreal (IVT) injection. Methods: New Zealand White (NZW) rabbits were intravitreally injected in both eyes with an injectable formulation in 5 (3 PK and 2 tolerability) studies. The rabbits received up to approximately 220?μg sirolimus per eye. At the desired timing post-injection, the animals were euthanized; both eyes were enucleated, frozen, and dissected to separate sclera, retina/choroid, and vitreous humor (VH). Whole blood (WB) samples were obtained at each time point before euthanasia. In clinical trials, patients received an IVT injection of approximately 352?μg sirolimus. Sirolimus concentrations in ocular tissues and WB samples were measured using liquid chromatography/tandem mass spectrometry (LC/MS/MS). In both single- and repeat-dose tolerability studies, systemic and ocular adverse effects were evaluated. Results: After IVT administration, sirolimus formed a depot in the VH. During dissolution, concentrations in VH were dose related and exhibited continuous release from the depot. This was characterized by a gradient of sirolimus concentration in the order of VH > retina/choroid > sclera > WB, and the concentrations were maintained for approximately 2 months after the IVT injection. After repeat dosing (132?μg), no drug accumulation was seen in the ocular tissue or systemically. In clinical studies, the highest blood levels were <2?ng/mL at day 2, and half-time (t(1/2)) was 8-9 days. There was no accumulation at day 30 after the IVT injection (up to 352?μg). Safety studies conducted on rabbits indicated good local tolerability. Sirolimus-related effects were limited to minor incipient cataract findings and mild lenticular changes. In the clinical studies where sirolimus was intravitreally administered up to 352?μg, injections were well tolerated. Conclusions: Sustained IVT delivery was achieved in a dose-dependent fashion after the IVT injection of a proprietary sirolimus depot-forming ocular formulation. Across the tolerability and safety studies, no significant findings were observed for systemic and ocular tolerability. The human WB levels were well below the daily trough systemic blood level range required for systemic immunosuppression. An IVT injection of sirolimus has a PK and safety profile that is favorable for treating inflammatory conditions of the eye, such as non-infectious uveitis, and warrants further investigation in humans.     

苦参碱聚乳酸微球的缓释性和玻璃体腔注射的安全性研究

目的研究苦参碱聚乳酸微球（MAT-PLA-MS）的缓释性和玻璃体腔注射的安全性。方法透射电镜观察MAT—PLA—MS的形态,紫外分光光度法观测其体外释放情况。玻璃体腔彩色照相记录其分解过程,裂隙灯显微镜、间接检眼镜、视网膜电图（ERG）、光学显微镜和透射电镜观察不同剂量组的苦参碱游离药物和MAT—PLA—MS在注药后不同时间点对眼组织的影响。结果MAT—PLA—MS的平均粒径为2．28μm,载药量为6．17％。体外释放672h,累积释放百分率为87．93％,缓释作用明显。MAT—PLA—MS在玻璃体腔内随时间延长表现为逐渐降解的过程。游离药物各剂量组和载药微球各剂量组在玻璃体腔注射后各时间点裂隙灯显微镜和间接检眼镜检查均未见异常。游离药物4mg组注药后1dERGb波振幅下降。组织病理学检查表明,游离药物4mg组在注药后1d开始出现视网膜毒性反应,载药微球6mg组在注药7d后出现轻微的视网膜毒性反应。结论MAT—PLA—MS具有明显的缓释效果,安全剂量较游离药物大,有望成为一种理想的防治增生性玻璃体视网膜病变的给药系统。     

Purtscher-like Retinopathy Associated with Systemic Lupus Erythematosus

Purpose: To report on clinical manifestations of Purtscher-like retinopathy (PLR) associated with systemic lupus erythematosus (SLE) and visual outcomes.

Methods: We performed a retrospective cohort study of 11 patients (21 affected eyes) with PLR in SLE.

Results: All patients were treated with systemic corticosteroids?±?immunosuppressive agents. Ocular therapy included intravitreal injections with bevacizumab in 18/21 eyes and posterior sub-Tenon injections with triamcinolone acetonide 13/21 eyes. Panretinal photocoagulation (PRP) was performed in 19/21 eyes and pars plana vitrectomy was required in 5/21 eyes. Visual improvement was found at follow-up of 3 and 6 months (p?=?0.05). Poor visual outcome was associated with presence of neovascularizations at onset (p?=?0.009), development of vitreous hemorrhage during PRP (p?=?0.015), and active status of SLE after onset of PLR (p?=?0.029).

Conclusions: PLR might manifest as a devastating complication of SLE. We recommend treating any systemic activity of SLE and starting an early ocular treatment.