Safety of intravitreal triamcinolone acetonide:an electrophysiologic and histopathological study in rabbits

AIM: To evaluate the retinal safety of various doses of intravitreal triamcinolone acetonide (TA) in rabbits.Methods: Thirty New Zealand albino rabbits were divided into five groups (six animals each). In group 1 (control group), each animal received a single intravitreal injection of 0.1mL phosphate buffered saline. In groups 2, 3, 4 and 5, each rabbit received a single intravitreal injection of 4, 8, 16 and 32mg of TA, respectively. Each dose was contained in 0.1mL phosphate buffered saline. Clinical ocular examinations were performed before the injection and on the 1st, 3rd, 10th and 17th post-injection days. A standard dark adapted electroretinogram (ERG) was obtained before injection and on the 3rd, 10th and 17th post-injection days. After 17d, animals were sacrificed and their eyes prepared for pathological examination.RESULTS:By monitoring ERG as a functional index for the retina, intravitreal injection of 4mg TA showed no significant ERG changes. At doses of 8, 16 and 32, hyper-abnormal responses in a- and b- waves of ERG were detected on the 3rd post-injection day. These changes gradually returned back to normal limits after 17d. Histopathological examination of the retina of all animals showed no pathological changes.CONCLUSION: High doses of intravitreal TA seemed to have enhancing effects on the retinal function with gradual return to normal limits with no pathological changes detected in examined eyes.     

Dose Dependent Effects of Intravitreal Triamcinolone Acetonide on Diffuse Diabetic Macular Edema

Purpose

To evaluate the effect of different doses of intravitreal triamcinolone acetonide on diffuse diabetic macular edema.

Methods

In a retrospective study, 44 eyes with diffuse diabetic macular edema were treated with an intravitreal injection of 4 mg (n=12 eyes), 8 mg (n=17) or 25 mg (n=15) of triamcinolone acetonide (TA). Optical coherence tomography, best-corrected logMAR visual acuity and Goldmann tonometry were performed at baseline, 1 week, and 1, 3, 6, 9 and 12 months after treatment. Mean follow-up was 9.8 months (standard deviation=2.3) with a range of 5-12 months.

Results

The duration of intravitreal TA effects on macular thickness and visual acuity increased with increasing dosage. An observed increase in intraocular pressure induced by TA was not significantly associated with dosage.

Conclusions

In patients with diffuse diabetic macular edema who receive intravitreal TA, effects may last longer after a dosage of 25 mg, than after lower doses of 8 mg or 4 mg.     

Immediate intraocular pressure rise after intravitreal injection of ranibizumab and two doses of triamcinolone acetonide

AIM: To evaluate prospectively immediate intraocular pressure (IOP) changes after the intravitreal injection of ranibizumab, 2 and 4mg triamcinolone acetonide. METHODS: Patients who underwent intravitreal injection of 0.1mL (4mg) triamcinolone acetonide (TA, Group T4), 0.05mL (2mg) TA (Group T2) and 0.05mL (0.5mg) ranibizumab (Group R) comprised the study population. Overall, 229 eyes of 205 patients were injected. Fifty-four eyes (23.6%) were in Group T4, 69 eyes (30.1%) in Group T2 and 106 eyes (46.3%) in Group R. If IOP was less than 26mmHg immediately after the injection no further measurement was performed. If IOP was ≥26mmHg, IOP was remeasured till the reading was below 26mmHg at 5, 15 and 30 minutes. RESULTS: Immediately after the injection, the IOP of 28 eyes (51.9%) in Group T4, 22 eyes (31.9%) in Group T2 and 51 eyes (48.1%) in Group R were over 25mmHg. At 30 minutes, IOP of one eye (1.9%) in group T4, two eyes (2.9%) in group T2 and two eyes (1.9 %) in Group R were over 25mmHg. Immediate post-injection IOP was significantly higher in Group T4 and Group R when compared to Group T2 (P<0.001 and P<0.001, respectively). IOP was significantly higher in eyes without vitreous reflux when compared to those with vitreous reflux in all groups (P<0.001). CONCLUSION: IOP may remarkably increase immediately after the intravitreal injection of 2 or 4mg triamcinolone acetonide, and 0.5mg ranibizumab. Absence of vitreous reflux is the most important predicting factor for immediate IOP rise after the injection.     

Comparison Between Intravitreal Bevacizumab and Triamcinolone for Macular Edema Secondary to Branch Retinal Vein Occlusion

Purpose

To compare the effects of intravitreal bevacizumab to those of triamcinolone acetonide injection for the treatment of macular edema secondary to branch retinal vein occlusion.

Methods

This retrospective study included 50 eyes of 50 patients who received a single injection of intravitreal bevacizumab (1.25 mg/0.05 mL, 22 eyes) or triamcinolone acetonide (4 mg/0.1 mL, 28 eyes) as the only treatment for macular edema secondary to branch retinal vein occlusion; all patients had a post-injection follow-up duration of >24 weeks. Best corrected visual acuity (BCVA), intraocular pressure (IOP), and central macular thickness (CMT) by optical coherence tomography were measured for up to 24 weeks after injection.

Results

BCVA was improved at 1, 4, 8,12 weeks post-injection in the bevacizumab group, and at 1, 4, 8 weeks post-injection in the triamcinolone group. No significant difference was found between the two groups except at 12 weeks. CMT decreased significantly within each group, and no significant difference between groups was found. In the bevacizumab group, no elevated IOP was observed, whereas IOP was significantly increased at 4, 8, and 12 weeks after triamcinolone injection; IOP was therefore significantly different between the two groups.

Conclusions

Intravitreal bevacizumab is a comparatively simple treatment method that can effectively improve BCVA and reduce CMT without ocular and systemic complications. Consequently, intravitreal bevacizumab injections may be useful as both an alternative and primary treatment for macular edema secondary to branch retinal vein occlusion.     

Multifocal electroretinogram findings after intravitreal bevacizumab injection in choroidal neovascularization of age-related macular degeneration

Purpose

To evaluate the changes in multifocal electroretinogram (mfERG) and optical coherence tomography (OCT) after intravitreal bevacizumab injection in the treatment of age-related macular degeneration (AMD).

Methods

Twenty-one eyes with choroidal neovascularization secondary to AMD were studied before and after intravitreal bevacizumab injection for best corrected visual acuity (BCVA), OCT, and mfERG.

Results

The BCVA improved, while central macular thickness and total macular volume in OCT decreased after intravitreal bevacizumab injection (p = 0.03, 0.01, and 0.01, respectively). In mfERG, the amplitude of P1, and implicit time of P1 and N1 indicated a statistically significant improvement of retinal response after intravitreal bevacizumab injection.

Conclusions

There is a potential role for mfERG in evaluating the effect on retinal function of intravitreal bevacizumab injection.     

Cytomegalovirus Retinitis after Multiple Ocular Surgeries in an Immunocompetent Patient

Purpose

To describe the case of a 74-year-old man who developed cytomegalovirus (CMV) retinitis after multiple ocular surgeries.

Methods

Observational case report.

Results

A 74-year-old man who had a history of multiple ocular surgeries developed unilateral retinitis with whitening of the entire peripheral retina. A presumptive diagnosis of viral retinitis was considered, and polymerase chain reaction of the aqueous fluid was positive for CMV DNA. Laboratory examination revealed that the patient was completely immunocompetent. Moreover, the patient did not have any subtenon or intravitreal injection of triamcinolone acetonide (TA). The patient responded well to intravenous ganciclovir and oral valganciclovir.

Conclusion

CMV retinitis can occur to immunocompetent patients without local immunosuppression with TA injection.Key words: Cytomegalovirus retinitis, Immunocompetent patient, Multiple ocular surgeries     

Safety of intravitreal clindamycin in albino rabbit eyes

Purpose

To study the potential toxic effects of intravitreal clindamycin on the retina of albino rabbits, by assessing functional and morphological retinal changes.

Methods

Eight albino rabbits were included in the study. In each rabbit, 1 mg/0.1 ml clindamycin was injected into the vitreous of the right (experimental) eye, and 0.1 ml saline was injected into the vitreous of the left (control) eye. The electroretinogram (ERG) was recorded before injection, 3 days, 1, 2, and 4 weeks post-injection. The visual evoked potential (VEP) was recorded 4 weeks post-injection. Clinical examination was conducted at all time points. The eyes were enucleated at the termination of the follow-up period in order to prepare the retinas for histology in order to assess retinal structure.

Results

ERG and VEP responses that were recorded from the experimental eye at different times following intravitreal clindamycin injection were very similar to the corresponding responses that were recorded from the control eyes. Clinical examination was normal in all eyes, and no histological damage was observed.

Conclusions

Intravitreal injection of 1 mg clindamycin does not cause functional or morphological signs of retinal toxicity in albino rabbits, during a period of 4 weeks post-injection. These findings support the clinical use of 1 mg intravitreal clindamycin.

     

Macular edema formation and deterioration of retinal function after intravitreal bevacizumab injection for proliferative diabetic retinopathy

Purpose

To report a case of proliferative diabetic retinopathy (PDR) showing transient macular edema (ME) and deteriorated retinal function after intravitreal bevacizumab injection (IVB).

Methods and Results

A 53-year-old man received IVB (1.25 mg/0.05 ml) in both eyes for the treatment of PDR. There was no treatment-related complication. However, he complained of photopsia in both eyes 6 h after the injection. Slit-lamp examination revealed mild cellular infiltrations (1+) in the anterior chamber in both eyes. Optical coherence tomography showed ME formation in the left eye. Both full-field and multifocal electroretinography (ERG) revealed the deterioration of all parameters in both eyes compared with pretreatment. The inflammation in the anterior segment and ME disappeared 1 day after the injection. ERG parameters were improved 9 days after the injection, except for the N1 and P1 amplitude of multifocal ERG in the left eye.

Conclusion

We propose that patients who undergo IVB should be carefully informed and followed up for possible complications including temporal ME formation and retinal function deterioration.Key Words: Anti-vascular endothelial growth factor, Bevacizumab, Avastin, Multifocal electroretinography, Full-field electroretinography, Diabetic retinopathy, Optical coherence tomography, Macular edema     

Implementation of a nurse-delivered intravitreal injection service

Purpose

The purpose of this study was to introduce nurse-delivered intravitreal injections to increase medical retina treatment capacity.

Methods

Indemnity, clinical governance, training, planning, and implementation issues were addressed. The outcome measures were patient safety, patient experience, and clinic capacity.

Results

No serious vision-threatening complications were recorded in a consecutive series of 4000 nurse-delivered intravitreal injections. A Mann–Whitney test showed a significant increase in intravitreal injections (P=0.003) in the medical retina service after introduction of nurse-delivered intravitreal injections. The majority of patients accepted and were satisfied with a nurse-delivered intravitreal injection.

Discussion

Nurse-delivered intravitreal injections appear safe, acceptable to patients, and are an effective means to increase intravitreal injection capacity in medical retina clinics.     

Coat's-like exudation in rhodopsin retinitis pigmentosa: successful treatment with an intravitreal dexamethasone implant

Purpose

Role of intravitreal injection of dexamethasone implant (Ozurdex) for refractory macular thickening.

Methods

A case report of a 13-year-old boy with Rhodopsin-positive, CRB1-negative retinitis pigmentosa presenting with Coat''s-like exudative vitreoretinopathy and treatment-resistant cystoid macular oedema.

Results

A reduction in the macular thickening following a single injection of Ozurdex.

Conclusion

We present our experience in successful treatment of refractory macular oedema with intravitreal injection of dexamethasone implant resulting in clinically significant resolution of macular thickening.     

Multiphasic changes in systemic VEGF following intravitreal injections of ranibizumab in a child

Purpose

To investigate whether intravitreal ranibizumab injections administered to a child alter systemic plasma levels of total and free VEGF 165.

Methods

A 9-year-old child sustained a choroidal rupture from blunt trauma. He subsequently developed a secondary choroidal neovascular membrane, which was treated with five ranibizumab injections over a period of 8 months. Peripheral venous blood samples were taken at each visit over a period of 12 months and plasma was extracted. Plasma VEGF 165 levels were determined using enzyme-linked immunosorbent assay and were assayed both pre- and post-immunodepletion to remove complexed VEGF.

Results

Plasma VEGF 165 levels proved labile following intravitreal injection of ranibizumab. Levels increased by 30% above baseline following the first intravitreal ranibizumab injection, but then returned to baseline despite two subsequent injections. There was then a rebound increase of 67% in total plasma VEGF levels following a further injection, which remained above baseline for 12 weeks despite two further intravitreal ranibizumab injections. Baseline levels were re-attained 26 weeks after the final injection.

Conclusions

These results suggest intravitreal ranibizumab injections can cause significant, multiphasic changes in systemic VEGF levels. This may be of particular clinical significance in children as VEGF is known to be vital in the development of major organs, in addition to its role in the maintenance of normal organ function in adults.     

Short-term efficacy of intravitreal triamcinolone acetonide for macular edema secondary to retinal vein occlusion that is refractory to intravitreal bevacizumab

Aims:

To evaluate the 1-month efficacy of intravitreal triamcinolone acetonide (TA) in treating macular edema secondary to retinal vein occlusion (RVO) that was refractory to intravitreal bevacizumab.

Materials and Methods:

This retrospective, observational study included 23 eyes from 23 patients with macular edema secondary to RVO. Macular edema that did not respond to two or more consecutive intravitreal bevacizumab injections was treated with intravitreal TA. Central foveal thickness (CFT) and best-corrected visual acuity (BCVA) were compared before and one month after TA injection.

Results:

Fifteen eyes were diagnosed with central RVO, and eight eyes were diagnosed with branch RVO. All patients were previously treated with 2.4 ± 0.6 intravitreal bevacizumab injections. The TA injection was performed, on average, 5.8 ± 1.4 weeks after the last bevacizumab injection. The CFT before TA injection was 516.6 ± 112.4 μm and significantly decreased to 402.3 ± 159.7 μm after TA therapy (P < 0.001). The logarithm of the minimal angle of resolution BCVA was 0.72 ± 0.34 before TA therapy and was not significantly improved by the treatment (0.67 ± 0.35, P = 0.119), despite a decrease in CFT. However, seven eyes (30.4%) had a BCVA gain of one or more lines.

Conclusions:

Intravitreal TA therapy was beneficial in some patients with macular edema secondary to RVO that was refractory to intravitreal bevacizumab therapy. This study suggests that intravitreal TA should be considered as a treatment option for refractory macular edema.     

In vivo biocompatibility of a new cyanine dye for ILM peeling

Purpose

To investigate the biocompatibility of the new cyanine dye: 3,3′-Di-(4-sulfobutyl)-1,1,1′,1′-tetramethyl-di-1H-benz[e]indocarbocyanine (DSS) as a vital dye for intraocular application in an in vivo rat model and to evaluate the effects of this dye on retinal structure and function.

Methods

DSS at a concentration of 0.5% was applied via intravitreal injections to adult Brown Norway rats with BSS serving as a control. Retinal toxicity was assessed 7 days later by means of retinal ganglion cell (RGC) counts, light microscopy, optical coherence tomography (OCT), and electroretinography (ERG).

Results

No significant decrease in RGC numbers was observed. No structural changes of the central retina were observed either in vivo (OCT) or under light microscopy. ERGs detected a temporary reduction of retinal function 7 days after injection; this was no longer evident 14 days after injection.

Conclusions

DSS showed good biocompatibility in a well-established experimental in vivo setting and may be usable for intraocular surgery as an alternative to other cyanine dyes. In contrast to indocyanine green, it additionally offers fluorescence in the visual spectrum. Further studies with other animal models are needed before translation into clinical application.     

Effects of an Intravitreal Bevacizumab Injection Combined With Panretinal Photocoagulation on High-Risk Proliferative Diabetic Retinopathy

Purpose

To investigate the short-term effects of panretinal photocoagulation (PRP) combined with an intravitreal injection of Avastin® (bevacizumab) as an adjuvant to high-risk proliferative diabetic retinopathy (PDR).

Methods

The data was collected retrospectively from the eyes of high-risk PDR patients, which were divided into two groups. One eye was treated with only PRP (PRP only group) and the fellow eye of same patient was treated with both PRP and intravitreal bevacizumab injection (Adjuvant group). Best corrected visual acuity (BCVA), IOP (intraocular pressure), and new vessel (NV) size in fluorescein angiography were recorded immediately and at the six-week follow-up visit. Adverse events associated with intravitreal injection were investigated.

Results

Of 12 patients with high-risk PDR, five were male and seven were female. There were no statistically significant BCVA or IOP changes after treatment in either group (p=0.916, 0.888). The reduction of NV size was found in both groups, but NV size in the adjuvant group showed a greater decrease than that of the PRP only group (p=0.038). Three patients had adverse events after intravitreal injection. Two patients had mild anterior uveitis and one patient had a serious complication of branched retinal artery obstruction (BRAO).

Conclusions

Intravitreal bevacizumab injection with PRP resulted in marked regression of neovascularization compared with PRP alone. One serious side effect, BRAO, was noted in this study. Further studies are needed to determine the effect of repeated intravitreal bevacizumab injections and the proper number of bevacizumab injections as an adjuvant.     

Evaluation of pain during intravitreal Ozurdex injections vs intravitreal bevacizumab injections

Purpose

The purpose was to evaluate the pain associated with intravitreal Ozurdex injections, and to compare it with that associated with intravitreal bevacizumab injections.

Methods

The study included 57 eyes of 57 patients who received an intravitreal Ozurdex injection at our institution. Pain was measured by the visual analog scale (VAS). Additional parameters recorded included age, sex, indication for the injection, number of previous Ozurdex injections in the study eye, presence of diabetes mellitus, and lens status. Data were compared with a 2 : 1 sex- and age-matched control group of 114 patients who received intravitreal bevacizumab injections.

Results

Indications for injection included diabetic macular edema (40.4%) and macular edema secondary to central and branch retinal vein occlusion (28% and 31.6%, respectively). Pain scores on the VAS ranged from 0 to 90, with a mean of 20.8±20.3. There was no significant difference in pain between Ozurdex and bevacizumab injections. Pseudophakia was correlated with increased pain in Ozurdex injections.

Conclusions

This is the first series evaluating the pain associated with intravitreal Ozurdex injections. Despite a larger needle gauge and tunneled injection technique, intravitreal injection of Ozurdex is not associated with increased pain compared with bevacizumab. This finding may be a potential advantage for Ozurdex, and may serve to improve patient compliance with future long-term treatment protocols.     

Fast Resolution of Recurrent Pronounced Macular Edema following Intravitreal Injection of Dexamethasone 0.7 mg

Purpose

To report the fast resolution of recurrent pronounced macular edema due to central retinal vein occlusion (CRVO) within 72 h following intravitreal injection of dexamethasone 0.7 mg (Ozurdex®).

Methods

An interventional case report with optical coherence tomography scans and fluorescein angiographic pictures.

Results

A 69-year-old Caucasian man underwent intravitreal injection of dexamethasone 0.7 mg due to incomplete CRVO. He had previously undergone 6 intravitreal injections of bevacizumab 1.25 mg (Avastin®) and a C-grid laser photocoagulation over an interval of 16 months. After repeated recurrences of macular edema, the injection of dexamethasone reduced the macular edema from 570 μm preoperatively to 246 μm postoperatively within 72 h following the injection. Best-corrected visual acuity improved from 0.1 to 0.6 within the same interval.

Conclusion

Dexamethasone can lead to a very fast reduction of macular edema in patients with vision loss due to CRVO and may facilitate an immediate visual rehabilitation. Retinal anatomy and visual acuity may be restored even in long-standing, recurrent cases.Key Words: Central retinal vein occlusion, Dexamethasone 0.7 mg, Ozurdex®, Recurrent macular edema     

Macular atrophy after combined intravitreal triamcinolone and photodynamic therapy to treat choroidal neovascularization

AIM: To report the appearance of choriocapillaris atrophy after combined high dose intravitreal triamcinolone acetonide (TA) and photodynamic therapy (PDT) to treat choroidal neovascularization (CNV) associated with age related macular degeneration (AMD). METHODS: The present study was retrospective about non-randomized interventional case series. Fifty-one consecutive eyes with subfoveal (all types) CNV associated with AMD were treated by PDT and intravitreal (19.4±2.1)mg per 0.1mL TA at the Alicante Institute of Ophthalmology. The appearance of macular choriocapillaris and retinal pigment epithelium (RPE) atrophy was considered at two years follow-up. Thirty consecutive eyes treated by PDT alone, matched for age, sex, and type and size of CNV were considered as control group. RESULTS: Twenty-one of 47 eyes in the study group (45%) and 7 of 30 eyes in the control group (23%) developed macular RPE and choriocapillaris atrophy in the treated area at month 24 (P=0.04, Chi-square test). The greatest diameter of the atrophic areas averaged (5044±1666)μm in the study group vs (4345±1550)μm in the control group. Mean final best corrected visual acuity (logarithm of minimal angle of resolution) was (0.87±0.33) in the cases with RPE atrophy vs (0.66±0.26) in the cases with no RPE atrophy in the study group (P=0.11, Mann-Whitney U test). CONCLUSION: The association of high doses of intravitreal TA and PDT may increase the risk for RPE and choriocapillaris atrophy.     

Acute-Onset Endophthalmitis Caused by Alloiococcus otitidis following a Dexamethasone Intravitreal Implant

Purpose

To report the first case of acute endophthalmitis caused by Alloiococcus otitidis after a dexamethasone intravitreal implant.

Methods

A 74-year-old female was treated with intravitreal Ozurdex^® in her left eye for central retinal vein occlusion (CRVO). Best-corrected visual acuity (BCVA) in the eye was 4/20. Intravitreal injection was uneventful. At 48 h after injection, she developed ocular pain and visual acuity had dropped to light perception. Endophthalmitis associated with intravitreal injection was suspected.

Results

The patient did not show a favorable clinical response following systemic, intravitreal, and topical fortified antibiotics. We then performed a vitreous biopsy and removed the Ozurdex implant by pars plana vitrectomy. A vitreous culture was positive for A. otitidis. At the 2-month follow up, no inflammation was observed, but due to CRVO and probably aggravated by endophthalmitis, the fundus showed macular fibrosis. The final BCVA was finger counting at 30 cm in her left eye.

Conclusions

In cases of an intravitreal implant associated with endophthalmitis, we recommend removal of the device because it may act as a permanent reservoir of organisms if it remains in the vitreous cavity.Key words: Alloiococcus otitidis, Dexamethasone implant, Endophthalmitis, Ozurdex     

Intravitreal injection of methotrexate in an experimental rabbit model: Determination of ultrastructural changes

Purpose:

To investigate the ultrastructural changes of the rabbit retina induced by intravitreal methotrexate injection.

Materials and Methods:

Ten New Zealand white rabbits were enucleated bilaterally at different time periods after intravitreal methotrexate injection. One rabbit was used as control group and one rabbit was used as intact group. Histopathological examinations were performed under light and electron microscopy. Early (within first three days after injection) and long-term (one month after serial injections) effects of intravitreal methotrexate on the retina were investigated.

Results:

Retinal edema, vacuolization, and disintegration of mitochondria of the retinal cells were observed as early changes. The main long-term effects after serial injections were edema in the photoreceptor, inner nuclear, and ganglionic cell layers. Cellular disorganisation was seen on light microscopy. Electron microscopic examination revealed mitochondrial degeneration and vacuole formation in retinal cells, nuclear degeneration in outer nuclear layer, and membranous whorl formation in photoreceptor and nerve fiber layers.

Conclusions

High dose intravitreal methotrexate injection may cause significant ultrastructural changes in the rabbit retina in varying severity. This finding may highlight the potential side effects of methotrexate on human retina in higher doses.