Therapeutic Effect of Guggulsterone in Primary Cultured Orbital Fibroblasts Obtained From Patients with Graves' Orbitopathy.

Purpose: Inflammation, hyaluronan production, and adipogenesis are the main pathological events leading to Graves' orbitopathy (GO). Guggulsterone (GS), a phytosterol found in the resin of the guggul plant, is a well-known treatment for several inflammatory disorders, such as arthritis, obesity, and hyperlipidemia. Here we investigated the effects of GS treatment on GO pathology. Methods: Using primary cultures of orbital fibroblasts from GO patients and non-GO controls, we examined the effects of GS on hyaluronan production and the production of proinflammatory cytokines induced by interleukin (IL)-1ß, using real-time reverse transcription-polymerase chain reaction analysis, western blots, and enzyme-linked immunosorbent assays. Further, adipogenic differentiation was evaluated by quantification of Oil Red O staining and assessment of protein levels of peroxisome proliferator activator gamma (PPARγ), CCAAT-enhancer-binding proteins (C/EBP) α and ß, and sterol regulatory element-binding protein-1 (SREBP-1). Results: Treatment with noncytotoxic concentrations of GS resulted in the dose-dependent inhibition of IL-1ß-induced inflammatory cytokines, including IL-6, IL-8, MCP-1, and COX-2, at both mRNA and protein levels. The hyaluronan level was also significantly suppressed by GS. Moreover, GS significantly decreased the formation of lipid droplets and expression of PPARγ, C/EBP α/ß, and SREBP-1 in a dose-dependent manner. GS pretreatment attenuated the phosphorylation of nuclear factor-kappa B induced by IL-1ß. Conclusions: Our data show significant inhibitory effects of GS on inflammation, production of hyaluronan, and adipogenesis in orbital fibroblasts. To our knowledge, this is the first in vitro preclinical evidence of the therapeutic effect of GS in GO.

A prospective comparison of the efficacy of 0.5% bupivacaine vs 0.75% ropivacaine in peribulbar anesthesia for vitreoretinal surgery.

Purpose: To date, there is no information on the comparison of the effect of 0.5% bupivacaine with 0.75% ropivacaine solution for vitreoretinal surgery. The aim of the study was to: compare the efficacy of 0.5% bupivacaine with 0.75% ropivacaine in peribulbar anesthesia for vitreoretinal surgery. This was a prospective randomized double-blinded observational study in a hospital setting. Sixty patients planned for vitreoretinal surgery were randomized into two groups based on the peribulbar injection administered either with 0.5% bupivacaine or 0.75% ropivacaine solution, as Group B (n = 30) and Group R (n = 30), respectively. Time of onset of analgesia, akinesia, and the need for supplemental anesthesia were noted. Student's t-test or Mann-Whitney U test were used for comparing continuous variables and Chi-square or a Fischer exact test were used as appropriate for comparing two proportions. Results: The patients in Group R showed an earlier onset of both, analgesia (1.97 min vs. 2.10 min, P = 0.002) and akinesia (2.77 min vs. 4.20 min, P < 0.001) compared with the patients in Group B. The efficacy of the block attained was Grade 5 (adequate anesthesia and akinesia without supplementation) in about 97% of the patients in Group R while only 90% in Group B. However, the differences between the groups for the efficacy of the block were not statistically significant (P = 0.301) neither for Grades 5 nor for Grade 4 and 3 (P = 1.00 for both). The onset of postoperative pain was similar for both groups (P = 1.00). Conclusion: We concluded that 0.75% ropivacaine is a better choice of local anesthetic solution for patients undergoing primary vitreoretinal surgery compared with 0.5% bupivacaine.

Development of a Novel Thyroid Function Fluctuated Animal Model for Thyroid-Associated Ophthalmopathy.

BACKGROUND: The establishment of a suitable and stable animal model is critical for research on thyroid-associated ophthalmopathy (TAO). In clinical practice, we found that patients treated with I-131 often exhibit TAO; therefore, we aimed to establish a novel thyroid function fluctuated animal model of TAO by simulating the clinical treatment process. METHODS: We treated SD rats with I-131 to damage the thyroid and then used sodium levothyroxine (L-T4) to supplement the thyroid hormone (TH) levels every seven days, leading to a fluctuating level of thyroid hormones that simulated the status of clinical TAO patients. Rats administered normal saline were considered as a control. The weight, intraocular pressure, and serum T3, T4, TSH and TRAb levels of the rats were measured, and the pathological changes were analyzed by H&E staining and transmission electron microscopy (TEM). RESULTS: The experimental rats (TAO group) exhibited significantly reduced weight and elevated intraocular pressure compared with the control rats. Meanwhile, the serum levels of T3 and T4 were up-regulated in the TAO group, but the TSH level decreased during the 10-week study. Moreover, increased numbers of blood vessels and inflammatory cell infiltrations were observed in the orbital tissues of the TAO rats, while no abnormal changes occurred in the control rats. The orbital myofibrils in the TAO rats appeared fractured and dissolved, with twisted structures. Mitochondrial swelling and vacuoles within the endoplasmic reticulum, swelling nerve fibers, shedding nerve myelin, and macrophages were found in the TAO group. CONCLUSION: Rats treated with I-131 and sodium levothyroxine exhibited characteristics similar to those of TAO patients in the clinic, providing an effective and simple method for the establishment of a stable animal model for research on the pathogenesis and treatment of TAO.

Anatomical position of hyaluronic Acid gel following injection to the infraorbital hollows.

PURPOSE: To examine with histology the anatomical location of hyaluronic acid gel injected to the infraorbital hollows of cadaver specimens. METHODS: The authors dissected 5 fresh hemifacial cadaver specimens following preperiosteal injection of hyaluronic acid gel to the infraorbital hollows. Following tissue fixation, full-thickness soft tissue sections were obtained along the medial, central, and lateral lower eyelid/midface of each specimen. Histologic examination of the anatomical location of hyaluronic acid gel was performed using hematoxylin and eosin and Hale colloidal iron stains. RESULTS: Histologic examination of the central and lateral lower eyelid/midface sections revealed a significant portion of hyaluronic acid gel in either a postorbicularis or a subcutaneous plane in 8 of 10 sections. Only 2 sections displayed hyaluronic acid gel solely within a preperiosteal plane. The medial sections revealed hyaluronic acid gel resting in either a preperiosteal or an intraorbicularis plane. Soft tissue structures such as deep fat compartment septa and the orbicularis oculi muscle appeared to play a significant role in influencing the resting position of hyaluronic acid gel. CONCLUSIONS: In most specimens, the location of a significant portion of hyaluronic acid gel following injection to the infraorbital hollows differed from the intended injection plane. Soft tissue structures including fat compartment septa and the orbicularis oculi muscle appear to influence the resting position of hyaluronic acid gel. Careful attention should be used to avoid overfilling the thin soft tissue layers of the medial infraorbital hollows or tear trough.

Double-blind, bilateral pain comparison with simultaneous injection of 2% lidocaine versus buffered 2% lidocaine for periocular anesthesia.

PURPOSE: Determine if raising the pH of 2% lidocaine with epinephrine 1:100 000 to a physiologic level decreases pain perception during periocular, subcutaneous anesthesia. DESIGN: Double-blind, prospective, randomized study. Simultaneous unilateral injections of buffered and unbuffered lidocaine solutions were given before surgery to patients having bilateral, periocular surgery. PARTICIPANTS: Fifty-four consecutive patients (27 male and 27 female; mean age, 68 years; standard deviation, 11 years). INTERVENTION: Patients were given simultaneous injections of buffered and unbuffered 2% lidocaine with epinephrine 1:100 000. The needles were inserted simultaneously and the anesthesia was injected for a 20-second count for a total volume of 1.0 ml per injected side. MAIN OUTCOME MEASURES: After the simultaneous injections, the patients were asked to rate the pain on each side on a Likert-type visual analog scale of 0 to 10. RESULTS: Sixty-five percent of patients preferred the buffered lidocaine with a scaled pain reduction of 0.9 (P = 0.0005). Additionally, for the patients who believed that the buffered solution was less painful, the mean decrease in scaled pain rating was 2, for a 51% reduction in pain level (P = 0.001). No gender differences were noted. CONCLUSIONS: Buffering 2% lidocaine with epinephrine 1:100 000 with sodium bicarbonate 8.4% offers a clinically and statistically significant reduction in pain experienced by two-thirds of patients receiving periocular subcutaneous anesthesia.

Histologic features of mesotherapy-induced orbital fat inflammation.

A 67-year-old man developed acute orbital inflammation after receiving cosmetic mesotherapy (Lipo-Dissolve) to the inferior orbital fat compartments. The injection was intended to cause lipolysis and shrinkage of fat lobules with subsequent cosmetic improvement. Injections of a mixture of bile salts, phospholipid, and alcohol preservative bilaterally in inferior orbital fat lobules led to an acute inflammatory reaction characterized histologically 12 days later by mild lymphocytic infiltration, fat necrosis, and fibrosis in the target areas. Benign proliferation of peripheral nerve trunks consistent with a traumatic neuroma was also noted histologically on one side. Inflammation including fat necrosis and traumatic neuroma are all possible consequences of mesotherapy.

Peribulbar and retrobulbar combined anesthesia for vitreoretinal surgery using ropivacaine.

PURPOSE: To evaluate the efficacy and clinical effects of local retrobulbar anesthesia using ropivacaine in vitreoretinal surgery. METHODS: Prospective study. A total of 919 vitreoretinal operations were followed. The operations were divided into three groups, depending on the degree of anesthesia needed. Group A: Vitrectomies with episcleral procedures (208 vitrectomies for detached retina or perforating trauma). Group B: Episcleral procedures only (410 operations for detached retina without vitrectomy). Group C: Vitrectomies without episcleral surgery (301 operations for macular pucker or hole, proliferative diabetic retinopathy, or silicone oil removal). Anesthesia was administered using a 23-gauge Atkinson-type retrobulbar needle, after topical anesthesia. Six mL of the solution containing 7.5 mg ropivacaine/mL were injected into the peribulbar space, and the other 4 mL deeper, into the retrobulbar space. The degree of infiltration of the palpebral region, the motor block in the extrinsic ocular muscles, and pain felt were checked and rated. RESULTS: Swelling of lids was seen in 885 patients (96%); in 21 (2%) swelling was partial. In 13 patients (1%) there were no signs of infiltration. The motor block was total in 801 (87%) eyes, while 118 (12%) had reduced ocular movements. The degree of anesthesia was as follows, considering the three groups together: no pain = 855 (93%) patients; moderate pain = 44 (4%) patients; very strong pain = 20 (2%) patients. No adverse events or side effects were observed. CONCLUSIONS: Ropivacaine used for retrobulbar-peribulbar combined anesthesia in vitreoretinal surgery showed excellent clinical efficacy as regards analgesia and muscle akinesia.

Visual experience during phacoemulsification under topical versus retrobulbar anesthesia: results of a prospective, randomized, controlled trial.

PURPOSE: To compare the subjective visual experience of cataract patients during phacoemulsification and intraocular lens implantation under topical anesthesia (TA) vs retrobulbar anesthesia (RA). DESIGN: Prospective, randomized, controlled trial. METHODS: Three hundred six cataract patients eligible for phacoemulsification and intraocular lens implantation were randomized to receive either TA or RA during surgery by one of three surgeons. The surgeons were familiar with both anesthetic techniques and operated on the patients using the technique to which the patients were randomized. A masked interviewer conducted in-person interviews with the patients using a standardized questionnaire about their intraoperative visual experience and their reaction to their visual experience between 30 minutes and 4 hours after the surgery. RESULTS: Two patients (one in each group) had intraoperative posterior capsule rupture and were excluded from analysis. There was no statistically significant difference between TA (n = 154) and RA (n = 150) groups, except that more males compared with females had TA (P = .03). More patients who had TA reported perception of light (P < .001) and colors (P < .001) and a change (either increase or decrease) in light brightness during the course of the surgery (P < .001). There was no statistically significant difference in the proportions of patients who saw movements, flashes, instruments, or the surgeon or medical staff during the operation and who found their visual sensations frightening in the two groups. However, 10.4% in the TA group and 9.3% in the RA group found their visual experience frightening. CONCLUSIONS: More patients undergoing cataract surgery under TA compared with RA reported perception of light, colors, and a change in light brightness. A significant proportion of patients in both groups found the visual experience frightening.

Combined topical and intracameral anesthesia in penetrating keratoplasty.

BACKGROUND: The standard of care for penetrating keratoplasty (PKP) is either retrobulbar or peribulbar anesthesia combined with seventh cranial nerve akinesia or general anesthesia. These methods are known to be associated with rare but potentially serious adverse ocular and systemic events. PURPOSE: To determine the safety and efficacy of combined topical and intracameral anesthesia in addition to intravenous sedation for repeat penetrating keratoplasty (PKP). SETTING: Tertiary-care university hospital. METHODS: In this prospective study, combined topical tetracaine 0.5% and 0.2 cc intracameral 1% lidocaine along with i.v. sedation with midazolam and fentanyl were used for patients undergoing repeat PKP in 15 eyes of 15 selected patients. The indication for surgery was failed corneal graft. Verbal pain scale (VPS, 0-3) was recorded preoperatively, intraoperatively at 3 time-points (after trephination, after placing 8 interrupted sutures, and after placing the running suture), and postoperatively (1 hour postoperatively, overnight pain, and 1 day postoperatively). Patient and surgeon satisfaction were assessed postoperatively using a scale (1-5). After surgery patients were asked for their preferences comparing the current use of topical anesthesia compared with retrobulbar anesthesia used for their initial PKP. RESULTS: The mean intraoperative VPS score was 0.51 +/- 0.32 (range 0-1.33), and the mean postoperative VPS score was 0.47 +/- 0.50 (range 0-1.67). There were no serious intraoperative or postoperative complications. All patients reported high mean satisfaction score of 4.67 +/- 0.49 (range 4-5). The mean satisfaction score reported by the surgeon was 4.47 +/- 0.63 (range 3-5). All patients but 1 (93.3%) preferred combined topical over retrobulbar anesthesia, which they had in their previous surgery. CONCLUSIONS: We found combined topical and intracameral anesthesia to be safe and effective in our selected group of patients undergoing repeat PKP, and it may provide a satisfactory alternative anesthetic modality for patients in whom general, retrobulbar, or peribulbar anesthesia may be contraindicated.

Central retinal artery occlusion after peribulbar anesthesia.

We describe the development of central retinal artery occlusion (CRAO) in 2 patients after peribulbar (periconal) anesthesia during uneventful phacoemulsification. Although peribulbar anesthesia avoids direct optic-nerve injury, indirect injury presenting as CRAO may occur from vasospasm in response to the injection.

Topical anesthesia for penetrating trabeculectomy.

PURPOSE: To evaluate the efficacy and clinical practicability of topical anesthesia in comparison with retrobulbar anesthesia for penetrating trabeculectomy. METHODS: The prospective single-surgeon clinical interventional trial included 20 consecutive patients, who were randomly distributed into a topical anesthesia group ( n=10) and a retrobulbar anesthesia group ( n=10). In the topical anesthesia group, patients received preoperatively oxybuprocaine 0.4% eye drops and cocaine hydrochloride eye drops 10%. The patients of the retrobulbar group received 5 ml mepivacaine 2% injected into the retrobulbar space. To assess intraoperative pain, each patient was asked immediately after surgery to quantitate his/her pain using a 10-point pain rating scale. RESULTS: The topical anesthesia group and the retrobulbar anesthesia study group did not vary significantly in duration of surgery (21.5+/-3.37 min vs 20.2+/-4.46 min, P=0.31), preoperative intraocular pressure (32.2+/-14.62 mmHg vs 30.6+/-12.33 mmHg, P=0.22), postoperative intraocular pressure (8.0+/-4.47 mmHg vs 9.12+/-3.13 mmHg, P=0.64), subjective pain score by the patient (2.25+/-1.23 relative units vs 2.33+/-1.08 relative units ( P= 0.71), and practicability score by the surgeon (2.24+/-1.76 vs 2.56+/-1.58, P=0.82). CONCLUSIONS: In view of its clinical feasibility and its minimally invasive character, topical anesthesia may be an option for penetrating trabeculectomy.

Carticaine versus lidocaine for peribulbar anesthesia in cataract surgery.

PURPOSE: To compare carticaine 4% and lidocaine 2% for peribulbar anesthesia in cataract surgery. SETTING: Ain Shams and Cairo University Hospitals, Cairo, Egypt. METHODS: This prospective double-blind randomized study comprised 200 cataract patients assigned to 1 of 2 groups of 100 each based on type of anesthesia: carticaine 4% or lidocaine 2%. The efficacy, safety, and duration of the motor and the analgesic block produced by carticaine 4% adrenaline hyaluronidase mixture and lidocaine 2% adrenaline hyaluronidase mixture used as peribulbar anesthesia were compared. The mean time for satisfactory block, need for supplementary injections, incidence of intraoperative and postoperative pain, and postoperative complications were evaluated. The data were analyzed using the Student t test and Mann-Whitney U test for intergroup differences. The chi-square or Fisher exact test was used to assess eye movement scores, the need for supplementary injections, the onset of postoperative pain, and the incidence of postoperative complications. RESULTS: The mean time for satisfactory anesthesia was 7.5 minutes +/- 1.68 (SD) for lidocaine 2% and 2.5 +/- 1.53 minutes for carticaine 4% (P <.001). The need for supplementary injections was 28% in the lidocaine group and 4% in the carticaine group (P <.001). The mean onset of postoperative pain was 2.00 +/- 0.86 hours in the lidocaine group and 5.52 +/- 1.80 hours in the carticaine group (P <.05). There were no cases of postoperative neurotoxicity or extraocular muscle dysfunction in either group. CONCLUSIONS: Carticaine 4% adrenaline hyaluronidase mixture was an effective and safe agent for peribulbar anesthesia. It was more efficient than lidocaine 2% adrenaline hyaluronidase mixture in the onset and quality of anesthesia as well as postoperative analgesia.

Long-term endothelial cell loss after phacoemulsification: peribulbar anesthesia versus intracameral lidocaine 1%: prospective randomized clinical trial.

PURPOSE: To evaluate endothelial cell loss after phacoemulsification with posterior chamber intraocular lens implantation using peribulbar anesthesia or topical anesthesia combined with intracameral unpreserved lidocaine 1%. SETTING: Department of Ophthalmology, Charité, Humboldt-University of Berlin, Berlin, Germany. METHODS: Before and 20 months +/- 5.1 (SD) after surgery, specular microscopy was used to evaluate the number and morphology of endothelial cells in 78 eyes having peribulbar anesthesia or topical anesthesia combined with an intracameral injection of 0.15 cc unpreserved lidocaine 1%. RESULTS: The mean endothelial cell loss was 11.11% in the peribulbar group and 12.55% in the topical/lidocaine group. There was no statistically significant difference in the amount of endothelial cell loss or cell morphology between the 2 groups. CONCLUSION: The long-term postoperative endothelial cell course showed that topical anesthesia combined with an intracameral injection of 0.15 cc unpreserved lidocaine 1% is a safe alternative to peribulbar anesthesia.

Topical anesthesia with or without propofol sedation versus retrobulbar/peribulbar anesthesia for cataract extraction: prospective randomized trial.

PURPOSE: To evaluate the feasibility of intravenous sedation in addition to topical anesthesia during cataract extraction. SETTING: Helsinki University Eye Hospital, Helsinki, Finland. METHODS: Three hundred seventeen eyes of 291 consecutive patients having cataract surgery were prospectively randomized to receive topical (oxybuprocaine 0.4%, n = 96), combined (topical anesthesia and propofol sedation, n = 107), or retrobulbar/peribulbar (prilocaine 1.5%, n = 114) anesthesia. The intraoperative conditions were judged by the surgeon. A numerical scale (0 to 10) was used to assess the degree of pain during surgery. Outcome measures were the number of complications and adverse events registered perioperatively and 1 week postoperatively as well as Snellen visual acuity. RESULTS: The success of posterior chamber intraocular lens (IOL) implantation through a self-sealing clear corneal incision was 97.9%, 96.3%, and 98.2% in the topical, combined, and retrobulbar/peribulbar groups, respectively. There was no difference among the groups in pain during surgery, frequency of complications, or outcome measures. One week postoperatively, visual acuity was 20/40 or better in 81.7%, 78.5%, and 77.5% of eyes in the topical, combined, and retrobulbar/peribulbar groups, respectively. The surgeon reported significantly fewer difficulties in the retrobulbar/peribulbar group (9.8%) than in the topical (26.0%) (P =.004) or combined (21.0%) (P =.036) groups. Additional sedative/analgesic medication given intraoperatively was required significantly more often in the topical (15.6%) than in the retrobulbar/peribulbar group (2.6%) (P =.002). Patients with bilateral surgery preferred combined anesthesia over retrobulbar/peribulbar anesthesia; however, there was no significant difference in patient acceptance among groups in patients having unilateral surgery. CONCLUSION: Intravenous propofol sedation added to topical anesthesia did not improve the operative conditions or surgical outcome. Retrobulbar/peribulbar anesthesia ensured the best surgical conditions. Patients in all anesthesia groups reported high satisfaction. However, patients having bilateral surgery seemed to prefer combined anesthesia over retrobulbar/peribulbar anesthesia.

Topical plus intracameral lidocaine versus retrobulbar anesthesia in phacotrabeculectomy: prospective randomized study.

PURPOSE: To compare the efficacy and safety of topical and retrobulbar anesthesia for phacotrabeculectomy. SETTING: Hospital Ramón y Cajal, Madrid, Spain. METHODS: This prospective study comprised 60 patients (60 eyes) having phacotrabeculectomy surgery. Patients were randomly assigned to 1 of 2 groups receiving topical anesthesia plus intracameral lidocaine 1% or retrobulbar anesthesia. Patients were asked to document the discomfort they experienced during the administration of the anesthetic agent, during surgery, and postoperatively using a numeric pain scale. Complications and surgical conditions were also evaluated. RESULTS: The retrobulbar group reported significantly more discomfort during administration of the anesthetic agent than the topical group (P < .001). The topical group reported significantly more discomfort intraoperatively (P < .01). Eyelid squeezing and eyeball movement were more common in the topical group; however, neither was a problem to the surgeon. There was no difference in surgical conditions (P = .38) or the postoperative pain scores between the 2 groups (P = .06). One patient receiving topical anesthesia developed a suprachoroidal hemorrhage intraoperatively. CONCLUSIONS: Topical anesthesia supplemented with intracameral lidocaine was an effective alternative to retrobulbar anesthesia for phacotrabeculectomy. Although the degree of patient discomfort was significantly higher during surgery under topical anesthesia, the method avoids the pain and complications associated with a retrobulbar injection.

Effect of sub-Tenon's and peribulbar anesthesia on intraocular pressure and ocular pulse amplitude.

PURPOSE: To compare the effect of peribulbar and sub-Tenon's anesthesia on intraocular pressure (IOP) and ocular pulse amplitude (OPA) in the injected eye and the fellow noninjected (control) eye. SETTING: Tel Aviv Medical Center, Tel Aviv, Israel. METHODS: This prospective study measured IOP and OPA at baseline and 1 and 10 minutes after administration of lidocaine anesthesia in 40 consecutive adult patients having elective cataract surgery. RESULTS: The IOP remained stable throughout the study with both modes of anesthesia. One minute after injection of the anesthetic agent, the OPA was significantly decreased in the injected eyes in both the sub-Tenon's (24%; P < .05) and peribulbar (25%; P < .05) groups. The decrease in the OPA in the sub-Tenon's group (14%; P < .05) was detectable after 10 minutes in the control eyes. In the peribulbar anesthesia group, the OPA in the control eyes increased significantly (9%; P < .05) 1 minute after injection of the anesthetic agent, returning to preinjection levels 10 minutes after the injection. CONCLUSIONS: The OPA in the eyes in which lidocaine was injected decreased significantly in both the sub-Tenon's and peribulbar groups. These findings have implications for the management of patients whose ocular circulation may be compromised.