Bioabsorbable, subcutaneous naltrexone implants mitigate fentanyl-induced respiratory depression at 3 months-A pilot study in male canines.

The aim of this study is to determine if extended-release, bioabsorbable, subcutaneous naltrexone (NTX) implants can mitigate respiratory depression after an intravenous injection (IV) of fentanyl. Six different BIOabsorbable Polymeric Implant Naltrexone (BIOPIN) formulations, comprising combinations of Poly-d,l-Lactic Acid (PDLLA) and/or Polycaprolactone (PCL-1 or PCL-2), were used to create subcutaneous implants. Both placebo and naltrexone implants were implanted subcutaneously in male dogs. The active naltrexone implants consisted of two doses, 644 mg and 1288 mg. A challenge with IV fentanyl was performed in 33 male dogs at 97-100 days after implantation. Following the administration of a 30 µg/kg intravenous fentanyl dose, the placebo cohort manifested a swift and profound respiratory depression with a ~50% reduction in their pre-dose respiratory rate (RR). The BIOPIN NTX-implanted dogs were exposed to escalating doses of intravenous fentanyl (30 µg/kg, 60 µg/kg, 90 µg/kg, and 120 µg/kg). In contrast, the dogs implanted with the BIOPIN naltrexone implants tolerated doses up to 60 µg/kg without significant respiratory depression (<50%) but had severe respiratory depression with fentanyl doses of 90 µg/kg and especially at 120 µg/kg. Bioabsorbable, extended-release BIOPIN naltrexone implants are effective in mitigating fentanyl-induced respiratory depression in male canines at about 3 months after implantation. This technology may also have potential for mitigating fentanyl-induced respiratory depression in humans.

Fentanyl-induced respiratory depression in rodents is inhibited by bioabsorbable, subcutaneous naltrexone implants at 3.5 months.

The aim of this study is to determine if extended-release, bioabsorbable, subcutaneous naltrexone (NTX) implants inhibit respiratory depression after an IV injection of fentanyl. Bioabsorbable implants fabricated from two different release-controlling polymers, poly-D-L-lactide (PDLLA) and polycaprolactone (PCL), alone (placebo) or containing NTX, were subcutaneously implanted in Sprague Dawley rats. After 3.5 months of implantation, the rodents were administered an IV bolus of fentanyl through the tail vein. The placebo implant rats received a dose of 4 micrograms (mcg) - (10 mcg/kg/dose), while the NTX implanted animals received a dose of 8 mcg (20 mcg/kg/dose). The minimum active dose of fentanyl that caused a > 50 ± 2% depression in the respiration rate in the placebo implanted rodents was 4 mcg. The respiration rate of the placebo implanted rats dropped from 208 ± 14 breaths/minute at predose, to 84 ± 12 breaths/minute (p = 0.0003) at 2 min. In contrast, all NTX implanted animals easily tolerated twice the dose of 8 mcg of fentanyl without any significant reduction in respiration rate. The mean respiration rate = increased from 164 ± 22 breaths/minute at predose to 178 ± 17 breaths/minute (p = 0.24) at 2 min. The mean plasma concentrations of NTX, 3.5 months after implantation, ranged from 7.4 (±1.1) ng/mL to 80.3 (±37.5) ng/mL. Bioabsorbable implants containing NTX effectively blocked fentanyl-induced respiratory depression in rodents as compared with placebo implants, 3.5 months after implantation.

Low-Dose Intravitreal Methotrexate for Proliferative Vitreoretinopathy.

BACKGROUND AND OBJECTIVE: Proliferative vitreoretinopathy (PVR) has been mitigated by intravitreal methotrexate (MTX) 400 µg/0.1 mL in several studies. Here, we evaluate the results from a lower dose of MTX, 200 µg/0.05 mL. MATERIALS AND METHODS: We identified and reviewed records of patients with grade ≥C1 PVR who were treated with 200 µg/0.05 mL MTX injections: during PVR surgery and every 2 weeks thereafter. RESULTS: Twenty-four eyes met inclusion criteria with a mean of 5.6 injections and follow-up ranging 6 to 56 months. The retina was reattached in 19 of 24 eyes (79%) after a single surgery and in 5 of 24 eyes (21%) after one additional PVR surgery. Visual acuity improved from baseline logMAR 1.63 to 0.97 at 12 months (P < .001), with 5 of 20 achieving 20/60 or better and 16 of 20 achieving 20/200 or better. One eye developed a transient corneal abrasion that resolved within 1 week. CONCLUSION: Low-dose MTX (200 µg/0.05 mL) during and after PVR surgery resulted in good rates of retinal reattachment and visual acuity recovery. [Ophthalmic Surg Lasers Imaging Retina 2023;54(3):139-146.].

2,4-Dinitrophenol pharmacologically promotes retinal detachment in rabbits.

PURPOSE: The most difficult and unpredictable step of macular translocation surgery is creating the retinal detachment. The authors evaluated the efficacy of 2,4-dinitrophenol (2,4-DNP) to promote retinal detachment in the rabbit. METHODS: A vitrectomy was performed in each eye of a Dutch-belted rabbit. One eye was injected with 0.1 cc of a 5 mmol/L 2,4-DNP, the other eye with 0.1 cc of BSS+. After 30 minutes, the minimum aspiration pressure required to visibly elevate the retina was recorded. Four nonvitrectomized eyes received an intravitreal injection of either 0.1 cc of BSS+ or 5 mmol/L 2,4-DNP, and were enucleated and fixated for histopathologic examination. RESULTS: In the 12 masked eyes, the mean aspiration pressure decreased from 217 +/- 20 mmHg in the six BSS+ eyes to 117 +/- 20 mmHg in the six 2,4-DNP treated eyes (P = 0.0022). A retinal detachment was present in three of six masked and two of two unmasked 2,4-DNP treated eyes and none of eight BSS+ treated eyes. There was no short-term toxicity to the retina at the light microscope level. CONCLUSION: Intravitreal injection of 2,4-DNP reduced the retinal adhesive force by over 50% when compared to the BSS+ treated control eyes, without any short-term retinal toxicity.

Macular infarction after transpupillary thermotherapy for subfoveal choroidal neovascularization in age-related macular degeneration.

PURPOSE: To report the complication of macular infarction after transpupillary thermotherapy (TTT) for the treatment of subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). DESIGN: Interventional case reports. METHODS: Among 107 consecutive patients with subfoveal CNV due to AMD, a 73-year-old woman with recurrent subfoveal classic choroidal neovascularization and a 76-year-old man with subfoveal occult choroidal neovascularization with adjacent areas of geographic retinal pigment epithelium atrophy noted a severe decrease in visual acuity and photopsias within hours of undergoing TTT. RESULTS: Both patients had marked whitening of the macula clinically and closure of the perifoveal capillaries on fluorescein angiography. Immediately after treatment their visual acuity decreased from 20/200 to 6/200 and from 20/400 to 2/200, respectively. Several months later, all exudation had resolved and their visual acuity had stabilized at 20/100 and 20/200, respectively. CONCLUSIONS: Macular infarction is a rare complication that occurred in two of 107 patients undergoing TTT for subfoveal CNV due to AMD. The presence of geographic retinal pigment epithelium atrophy or a previous laser treatment scar in the macular region may predispose patients to this complication.

Limited macular translocation for atrophic maculopathy.

OBJECTIVES: To report visual improvement following bilateral limited macular translocation for a patient with atrophic macular disease, and to discuss issues related to the selection of potential candidates for this technique. DESIGN: Case report. RESULTS: A 78-year-old woman with bilateral atrophic maculopathy and no choroidal neovascularization had slowly progressive loss of visual acuity for at least 17 months in the right eye and 25 months in the left eye. She underwent bilateral limited macular translocation, using scleral infolding in the right eye and scleral outpouching in the left eye. Following translocation of her maculae, her best-corrected visual acuity improved from 20/200 to 20/30 OD and from 20/180 to 20/100 OS. She remained stable during 30 months of follow-up for the right eye and 22 months of follow-up for the left eye. CONCLUSION: Macular translocation may allow visual recovery in selected patients with atrophic maculopathy, even after a prolonged period of poor vision.