Freeze-dried matrices for ocular administration of bevacizumab: a comparison between subconjunctival and intravitreal administration in rabbits.

This work was aimed to tune solid matrices for bevacizumab (BVZ) subconjunctival or intravitreal administration in order to prolong drug release, to reduce the number of applications and consequently the side effects. Matrices, with sizes suitable for intravitreal or subconjunctival administration, based on hydroxypropylmethyl cellulose (HPMC), polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) and polyacrylic acid (PAA) were obtained by freeze-drying of polymeric dispersions either in phosphate buffer solution or water and were sterilized by gamma rays. The matrices were characterized from the technological point of view and evaluated for in vitro release of dextran and BVZ. In vivo evaluation of BVZ release in ocular humours was finally carried out on rabbits. The obtained matrices showed solvent sorption time ranging from a few seconds for PAA to 46 min for HPMC, with shorter times when prepared in buffer solution. The hydration times were up to 5.5-fold higher after sterilization. HPMC and PVA matrices showed a slowdown of the release rate of both dextran and BVZ, but HPMC was selected for following in vivo studies also in consideration of its higher viscosity after rehydration of the matrix. HPMC matrix was well tolerated by the rabbit eye when intravitreally and subconjunctivally administered. The different treatment produced the same effect in terms of drug concentration in aqueous and vitreous humour up to 12 weeks after administration. The results of this study support the possible use of lyophilized matrices as a BVZ delivery system to the posterior segment of the eye.

Heavy silicone oil (Densiron-68) for the treatment of persistent macular holes: Densiron-68 endotamponade for persistent macular holes.

PURPOSE: To evaluate the efficacy and safety of the use of Densiron-68 as intraocular endotamponade for the treatment of persisting macular holes (persistent MHs). METHODS: Retrospective interventional case study on 23 consecutive eyes showing persistent MHs after unsuccessful primary surgery that underwent retreatment with pars plana vitrectomy and Densiron-68 filling. The main outcome measures were: anatomic closure evaluated with optical coherence tomography (OCT), final best-corrected visual acuity (BCVA), and postoperative complications. RESULTS: A total of 23 patients (52-88 years) were studied. Pre-operative OCT showed full-thickness MH (mean size 560 microm) in all patients. Densiron-68 was left in situ for 1.5-3 months. Final follow-up time was 12 months after the last surgery. Postoperative OCT showed the complete closure of the PMH in 20 of 23 eyes. Pre-operative BCVA ranged from 20/200 to 20/630 (1.50-1.00 logMAR, mean 1.14). Final postoperative BCVA ranged from 20/30 to 20/400 (0.18-1.30 logMAR, mean. 0.61). Nineteen eyes (82%) showed a significant increase in visual acuity by at least three lines: 11 (47%) patients gained at least four lines. Three eyes remained unchanged (13%). One case deteriorated by two lines (4%). No major complications were recorded. CONCLUSIONS: Retreatment with Densiron-68 filling was safe and achieved encouraging anatomic and functional results.

Injection of intravitreal bevacizumab (Avastin) as a preoperative adjunct before vitrectomy surgery in the treatment of severe proliferative diabetic retinopathy (PDR).

PURPOSE: To evaluate the use of preoperative intravitreal bevacizumab (IVB) in patients undergoing pars plana vitrectomy (PPV) for complications of proliferative diabetic retinopathy (PDR). METHODS: We studied 22 patients with severe PDR. A preoperative complexity score (CS) was recorded. Eleven eyes were treated with IVB, 1.25 mg, 5-7 days before PPV (group 1), and 11 eyes underwent direct PPV (group 2). Surgical time and intra-operative manoeuvres were recorded. Main outcome measure was feasibility of surgery, secondary goal was the visual and anatomic outcome at 6 months. RESULTS: The average CS was 5.5, and was similar in the two groups. Mean surgical time was 57 minutes in group 1 vs 83 minutes in group 2; mean tool exchanges was 27 vs 53, intraoperative bleeding 5 vs 15, endodiathermy 2 vs 9. No complications were recorded after IVB. Mean pre-operative BCVA was 1.87 logMAR in group 1 and logMAR 2.04 in group 2. Mean pre-operative BCVA was 1.87 logMAR in the bevacizumab group and 2.04 logMAR in group 2, not significantly different (p = 0.7). Mean post-operative BCVA at 6 months was 0.88 logMAR in group 1 and logMAR 2.01 in control group 2, significantly different (p = 0.01). Post-operative BVCA improved in bevacizumab group from pre-operative value (p = 0.15), while in control group there was non-significant increase (p = 0.96). Anatomical attachment was achieved in 11 patients in group 1 vs nine patients in group 2. CONCLUSIONS: IVB administered prior to vitrectomy was well tolerated and reduced active neovascularization, thus facilitating PPV.

A new heavy silicone oil (HWS 46-3000) used as a prolonged internal tamponade agent in complicated vitreoretinal surgery: a pilot study.

PURPOSE: To report the results of a prospective pilot study using a new heavy agent, HWS 46-3000, as long-term endotamponade in complicated retinal detachment. METHODS: Thirty-two consecutive patients were enrolled in the study. Indications for enrollment included retinal detachment with proliferative vitreoretinopathy arising from inferior or posterior tears. The patients underwent pars plana vitrectomy, membrane peeling, and HWS 46-3000 filling. Follow-up examinations were scheduled at 1 day to 7 days and 1 month to 3 months after initial surgery and 7 days and 1 month to 6 months after endotamponade removal. RESULTS: At baseline examination, mean best-corrected Snellen visual acuity was 2.44 logarithm of the minimal angle of resolution (logMAR). HWS 46-3000 was removed after 45 days to 96 days. Initial retinal reattachment was achieved in all eyes. HWS 46-3000 endotamponade was associated with a success rate of 84.6% with a single surgery and an overall success rate of 100% at 6 months with the second operation and conventional silicone oil endotamponade. At 6 months, mean best-corrected visual acuity was +1.09 logMAR (P < 0.0001). Complications were posterior subcapsular cataract formation (100%), membrane formation (3 eyes, 9%), and increased intraocular pressure (1 eye). Emulsification and intraocular inflammation were not observed. CONCLUSION: HWS 46-3000 was well tolerated, effective in the inferior quadrants with a low incidence of membrane development. The main complication was the high rate of tamponade-related cataract formation.

Modified incision in 25-gauge vitrectomy in the creation of a tunneled airtight sclerotomy: an ultrabiomicroscopic study.

BACKGROUND: The standard straight incision for 25-gauge vitrectomy may not close well at the end of surgery with post-operative hypotony. To overcome incompetent wound closure, oblique insertion of the trocars has been suggested. More recently we have developed an oblique incision. which is parallel to the scleral fibres instead of perpendicular and therefore avoids cutting. The aim of this study was to compare the effectiveness of the different incisions and to investigate their behaviour with the UBM. METHODS: 45 patients affected by macular holes were operated; in 15 eyes using oblique-parallel insertion (OPAI), in 15 oblique-perpendicular (OPEI) and in 15 straight incision (SI). Patients underwent UBM examinations 1 day, 1 week, 1 month p.o. RESULTS: OPAI was airtight after the removal of 25 g cannulas. UBM examination 1 day post-operatively (p.o) showed the 45 sclerotomies were well healed with perfect apposition of the internal wound lips. 39 sclerotomies were undetectable, 6 slightly evident. With OPEI the incisions were airtight at the end of surgery. At the 1 day p.o. UBM examination the 45 sclerotomies were well-healed but a minimal gape was clearly visible in all of them, 3 eyes showed peripheral cilio-choroidal (CCD) detachment, which was resolved after 7 days although the gape was still evident. At 1 month p.o. examination the gape was not detectable in 20 sites, evident in 25. With SI at the end of the surgery conjunctival bleb formation was detected in 10 cases, air-gas refilling was performed in 7 eyes and 3 sclerotomies were sutured. At 1 day p.o. hypotony was recorded in 5 patients, recovering at the 7 day follow-up. At the 1 day p.o. UBM examination showed a significant gape in all sites, weak vitreous entrapment was shown in 36, subconjunctival fluid in 4, CCD in 7. At the 7 day UBM the CCD had disappeared in 4 and was reduced in 3. At the 1 month p.o. the sclerotomy defect was still detectable but other complications were no longer evident. CONCLUSIONS: OPAI achieved the quickest and most complete sealing since the 1st day p.o without complications, therefore it could be safer when performing 25-g vitrectomy with extensive manipulation.

Successful treatment of persistent macular holes using "heavy silicone oil" as intraocular tamponade.

BACKGROUND: Silicone oil tamponade has been suggested in the treatment of persistent macular hole, but visual outcome is often poor. We describe two patients who underwent reoperation for persistent macular hole using "heavy silicone oil" (HSO) tamponade. METHODS: Two patients who underwent vitrectomy, removal of the posterior vitreous cortex, peeling of the internal limiting membrane, and long-acting gas tamponade had persistent macular hole 3 months after surgery. The patients underwent reoperation using an HSO (Oxane Hd, Bausch & Lomb) as internal tamponade. This tamponade did not require postoperative posturing and was removed after 3 months. Optical coherence tomography (OCT) was performed, and visual outcome was determined. RESULTS: OCT images showed that the HSO bubble conformed well with the retinal surface in the foveal region. Closure of the macular hole was achieved in both patients. Visual acuity increased from 20/100 to 20/40 in Patient 1 and from 20/600 to 20/100 in Patient 2. CONCLUSION: HSO can be a useful tool in the treatment of persistent macular hole. OCT images showed that the tamponade was effective in the upright position in the foveal region. OCT allowed determination of the time of tamponade removal according to the anatomical stage of hole closure.

Modified technique for safer indocyanine-green-assisted peeling of the internal limiting membrane during vitrectomy for macular hole repair.

BACKGROUND: During macular hole surgery, indocyanine green (ICG) has access to the subretinal space and can lead to toxic and phototoxic damage of the retinal pigment epithelium (RPE). To reduce its toxicity and to avoid contact between ICG and the RPE, we have developed a modified technique by using autologous whole blood. METHODS: Thirty-one eyes underwent vitrectomy for idiopathic macular hole repair. Autologous whole blood (0.1 ml) was injected into the buffered saline solution (BSS)-filled vitreous cavity over the posterior pole and aspirated with a flute cannula. A small clot remained covering the macular hole. The internal limiting membrane (ILM) was stained by using 0.05% ICG solution. The ICG was dissolved in 5% glucose to obtain an iso-osmotic solution. This ICG was injected into the BSS-filled vitreous cavity over the posterior pole and removed after 10 s. The ILM was peeled and a long-acting gas tamponade applied. Pre- and postoperative best-corrected visual acuity and optical coherence tomography (OCT) findings are reported. RESULTS: Macular hole closure was achieved in 30 of 31 eyes (97%). The mean preoperative logMAR acuity was 0.99 (range: 0.4 to 2.0). Mean postoperative logMAR acuity was 0.496 (range: 0.0 to 1.0). The average improvement in vision was 0.66 logMAR units (range: 1.5 to 0.0). No postoperative RPE alterations were observed biomicroscopically or on OCT. CONCLUSION: This surgical technique leads to favorable anatomic and functional results. ICG toxicity is reduced by modifying osmolarity, concentration and contact time and by injecting ICG under BSS. Autologous whole blood acts as a mechanical barrier and prevents ICG from entering in the subretinal space.

25-gauge, sutureless vitrectomy and standard 20-gauge pars plana vitrectomy in idiopathic epiretinal membrane surgery: a comparative pilot study.

BACKGROUND: The aim of the study was to evaluate the safety and functional outcome of a small incision, sutureless vitrectomy in the treatment of idiopathic epiretinal membranes (ERM) compared with a standard 20-gauge vitrectomy system. METHODS: Forty-six consecutive patients with idiopathic ERM were recruited for this study and prospectively evaluated. In group 1 (n=26) we used a transconjunctival sutureless 25-gauge vitrectomy system (TSV), patients in group 2 (n=20) were operated on using a standard 20-gauge vitrectomy system. The ERM was removed and the internal limiting membrane (ILM) was peeled in all eyes. Surgery-related complications, operating time, intraoperative balanced salt solution (BSS) consumption, postoperative discomfort, postoperative intraocular inflammation, lens opacification, and long-term visual outcome are reported and compared. RESULTS: No surgery-related complications were observed in either group. Operating time was shorter in group 1 compared with group 2 (mean 15.6 and 29.6 min respectively). Intraoperative amount of BSS consumption was less in group 1 (mean 28 ml in group 1 and 42 ml in group 2). Postoperative discomfort and intraocular inflammation were significantly reduced in the 25-gauge group. In the 20-gauge group cataract formation requiring surgery was observed in two eyes. Visual acuity improved significantly in both groups. The 25-gauge group improved on average by more lines of vision and the improvement in vision was more rapid. CONCLUSION: The TSV system is a safe and efficient surgical technique for ERM surgery. Operating time is significantly reduced, minimizing surgery-induced trauma, and reducing postoperative intraocular inflammation and the patients' discomfort. The incidence of cataract formation may be less using TSV. Postoperative recovery is accelerated.

A pilot study on the use of silicone oil-RMN3 as heavier-than-water endotamponade agent.

AIMS: This work was conducted to report an interventional non-comparative pilot study using Oxane HD, a mixture of ultra-purified silicone oil and RMN3, a partially fluorinated olefin, as heavier-than-water internal tamponade. METHODS: Twenty-eight consecutive patients were recruited for this study. Indications included recurrent retinal detachment (RD) with proliferative vitreoretinopathy (PVR) (stage > or =C2) arising from inferior or posterior tears, recurrences after vitreoretinal surgery, penetrating trauma and combined rhegmatogenous and choroidal detachment. The patients underwent a pars plana vitrectomy, membrane peeling, and Oxane HD was used as long-term internal tamponade. RESULTS: Oxane was removed after 88 days (range 45-96 days) and exchanged with BSS in five eyes, long-acting gas in 14 eyes and with silicone oil in nine eyes. Retinal reattachment was achieved in 15 eyes. The overall anatomical success rate obtained using Oxane HD was 53.5%. In 15 patients with previous marked scleral buckling, the success rate was 26%: in nine patients recurrent RD occurred in the inferior sector, in five patients new tears were detected in the lower sectors; membrane formation was observed in 15 eyes. In 13 patients without marked scleral indent, the success rate was 84.6%. There was no evidence of dispersion and excessive inflammation. CONCLUSION: Oxane HD may be a useful tool in complicated RD with large inferior breaks, inferior PVR or combined rhegmatogenous, and choroidal detachment without marked scleral buckling, which put the eye profile out of shape, led to a higher failure rate and reduced the tamponading effectiveness of Oxane HD.