Does early response to intravenous glucocorticoids predict the final outcome in patients with moderate-to-severe and active Graves' orbitopathy?

PURPOSE: Intravenous glucocorticoids (ivGCs) given as 12-weekly infusions are the first-line treatment for moderate-to-severe and active Graves' orbitopathy (GO), but they are not always effective. In this study, we evaluated whether response at 6 weeks correlated with outcomes at 12 (end of intervention) and 24 (follow-up) weeks, particularly in patients initially unresponsive. METHODS: Our database (Bartalena et al. J Clin Endocrinol Metab 97:4454-4463, 10), comprising 159 patients given three different cumulative doses of methylprednisolone (2.25, 4.98, 7.47 g) was analyzed, pooling data for analyses. Responses at 6 weeks were compared with those at 12 and 24 weeks using three outcomes: overall ophthalmic involvement [composite index (CI)]; quality of life (QoL); Clinical Activity Score (CAS). Responses were classified as "Improved", "Unchanged", "Deteriorated", compared to baseline. RESULTS: Deteriorated patients at 6 weeks for CI (n = 8) remained in the same category at 12 weeks and 7/8 at 24 weeks. Improved patients at 6 weeks for CI (n = 51) remained in the same category in 63% and 53% of cases at 12 and 24 weeks, respectively. Unchanged patients at 6 weeks (n = 100) eventually improved in 28% of cases (CI), 58% (CAS), 32% (QoL). There was no glucocorticoid dose-dependent difference in the influence of early response on later outcomes. CONCLUSIONS: Patients who deteriorate at 6 weeks after ivGCs are unlikely to benefit from continuing ivGCs. Patients unresponsive at 6 weeks still have a significant possibility of improvement later. Accordingly, they may continue ivGC treatment, or, alternatively, possibly stop ivGCs and be switched to a second-line treatment.

Ocular surface and tear film abnormalities in women under adjuvant chemotherapy for breast cancer with the 5-Fluorouracil, Epirubicin and Cyclophosphamide (FEC) regimen.

AIM: To study possible ocular surface and lacrimal drainage changes in women being on adjuvant chemotherapy with 5-Fluorouracil 600 mg/m2, Epirubicin 60-90 mg/m(2), Cyclophosphamide 600 mg/m(2) (FEC) regimen for breast cancer. METHODS: Sixty one consecutive women with early stage breast cancer (median age 58 years - interquartile range 22) were included in this study. They all underwent mastectomy followed by 6 cycles of tri-weekly administration of FEC regimen and were free of ocular surface, eyelid and tear film symptomatic disease at baseline. None of them had pre- or coexisting treatment with other chemotherapeutic agent or radiotherapy. Slit lamp examination of the ocular surface, Schirmer test I (without topical anesthesia) and tears Break up Time test (BUT) were performed before the initiation of treatment and immediately after the third therapeutic cycle. RESULTS: From 61 women 39.34% had significant conjunctival hyperemia, 41.0% lid margin abnormalities, 4.92% blepharitis, 6.56% madarosis, 3.28% punctate epithelial keratopathy and 4.92% oedema of the lower punctum mucosal opening after three chemotherapeutic cycles. Mean BUT measures were found lower after the third chemotherapeutic cycle (p=0.001) but mean Schirmer test I values were higher after the third chemotherapeutic cycle (p=0.001). CONCLUSION: Women on chemotherapy with FEC regimen are more susceptible to develop ocular surface and tear film alterations, within the first three cycles of chemotherapy for breast cancer, and thus, prompt ophthalmological evaluation may be proven beneficial for early diagnosis and management of the induced ocular disease.

Descemet's stripping endothelial automated keratoplasty using Tan EndoGlide endothelium insertion system.

PURPOSE: The purpose of this study was to evaluate early visual and refractive outcomes of Descemet's stripping endothelial keratoplasty (DSAEK). METHOD: Nine eyes of 7 male and 2 female patients, mean age 73 years, were treated with DSAEK. Eight had pseudophakic bullous keratopathy and 1 had advanced Fuch's syndrome. Patients were followed up for a mean of 11.4 months (range, 4-26). The DSAEK technique consisted of stripping Descemet's membrane and endothelium from a recipient cornea and transplanting the posterior stroma and endothelium of a donor cornea using the Tan EndoGlide. The mean operating time was 61.89 minutes (standard deviation [SD], 9.3). RESULTS: The median donor diameter was 8.375 mm (range, 8.25-8.75) and the mean donor thickness was 114.4 µm (range, 98-129). Mean preoperative sphere was -2.41 that changed postoperatively in -1.21. Mean endothelial cell loss was 25% (range, 23%-45%) at 6 months after surgery. Corneal pachymetry was reduced from 796.6 µm preoperatively to 535.5 µm postoperatively. Best corrected vicual acuity (BCVA) was 20/40 or better postoperatively and exceeded the preoperative BCVA in all eyes. No graft failure was present. Two partial graft dislocations (1st and 5th postoperative day) were observed. One graft was successfully attached after reinjecting an air bubble (rebubbling) in the anterior chamber and the other graft was reattached with 4 10/0 nylon sutures after failed rebubbling. CONCLUSIONS: The key to successful endothelial transplantation is the protection and preservation of as many donor endothelial cells as possible. The TAN EndoGlide is a device that consistently delivers a donor lenticule through a small incision with minimal endothelial loss, while making the insertion procedure relatively reliable and consistent, with the surgeon in full control of the donor at all stages of insertion. The endothelial cell loss during this technique is comparable (if not better) with other endothelial graft insertions systems.

Does the use of trypan blue during phacoemulsification affect the intraocular pressure?

OBJECTIVE: The purpose of the study was to evaluate the effect of trypan blue on intraocular pressure (IOP) after small-incision cataract surgery. DESIGN: Prospective, randomized study. PARTICIPANTS: Fifteen patients (30 eyes) with bilateral, dense, age-related cataracts. METHODS: Patients with glaucoma, ocular hypertension, exfoliation, pigment dispersion syndrome, history of uveitis, recent use of topical or systemic steroids, and previous ocular surgery were excluded. The patients were randomly assigned to receive trypan blue during cataract surgery for enhancing capsulorrhexis in 1 of their eyes, while in the other eye, trypan blue was not used. Cataract surgery was performed in an identical fashion in both eyes, with a sutureless posterior limbal incision, phacoemulsification, and implantation of a foldable intraocular lens. The same viscoelastic (sodium hyaluronate) was used in all cases and was thoroughly aspirated at the end of the procedure. All patients received a single dose of 250 mg acetazolamide 8 hours after surgery. No other antiglaucomatous agent was used during surgery or postoperatively. The intraocular pressure (IOP) was measured preoperatively and at 24 hours, 1 week, 1 month, and 3 months postoperatively. RESULTS: IOP values were similar in both groups at all 4 postoperative measurements. There was no statistically significant difference in postoperative IOP values between the eyes in which trypan blue was used and the control eyes. CONCLUSIONS: The use of trypan blue during small-incision cataract surgery does not have any effect on IOP during the immediate and early postoperative period.

Outcome of orbital decompression for disfiguring proptosis in patients with Graves' orbitopathy using various surgical procedures.

AIM: To compare the outcome of various surgical approaches of orbital decompression in patients with Graves' orbitopathy (GO) receiving surgery for disfiguring proptosis. METHOD: Data forms and questionnaires from consecutive, euthyroid patients with inactive GO who had undergone orbital decompression for disfiguring proptosis in 11 European centres were analysed. RESULTS: Eighteen different (combinations of) approaches were used, the swinging eyelid approach being the most popular followed by the coronal and transconjunctival approaches. The average proptosis reduction for all decompressions was 5.0 (SD 2.1) mm. After three-wall decompression the proptosis reduction was significantly greater than after two-wall decompression. Additional fat removal resulted in greater proptosis reduction. Complications were rare, the most frequent being worsening of motility, occurring more frequently after coronal decompression. The average change in quality of life (QOL) in the appearance arm of the GO-QOL questionnaire was 20.5 (SD 24.8) points. CONCLUSIONS: In Europe, a wide range of surgical approaches is used to reduce disfiguring proptosis in patients with GO. The extent of proptosis reduction depends on the number of walls removed and whether or not fat is removed. Serious complications are infrequent. Worsening of ocular motility is still a major complication, but was rare in this series after the swinging eyelid approach.

A questionnaire survey on the management of Graves' orbitopathy in Europe.

OBJECTIVE: To determine management patterns among clinicians who treat patients with Graves' orbitopathy (GO) in Europe. DESIGN AND METHODS: Questionnaire survey including a case scenario of members of professional organisations representing endocrinologists, ophthalmologists and nuclear medicine physicians. RESULTS: A multidisciplinary approach to manage GO was valued by 96.3% of responders, although 31.5% did not participate or refer to a multidisciplinary team and 21.5% of patients with GO treated by responders were not managed in a multidisciplinary setting. Access to surgery for sight-threatening GO was available only within weeks or months according to 59.5% of responders. Reluctance to refer urgently to an ophthalmologist was noted by 32.7% of responders despite the presence of suspected optic neuropathy. The use of steroids was not influenced by the age of the patient, but fewer responders chose to use steroids in a diabetic patient (72.1 vs 90.5%, P<0.001). Development of cushingoid features resulted in a reduction in steroid use (90.5 vs 36.5%, P<0.001) and increase in the use of orbital irradiation (from 23.8% to 40.4%, P<0.05) and surgical decompression (from 20.9 to 52.9%, P<0.001). More ophthalmologists chose surgical decompression for patients with threatened vision due to optic neuropathy, who were intolerant to steroids than other specialists (70.3 vs 41.8%, P<0.01). CONCLUSION: Deficiencies in the management of patients with GO in Europe were identified by this survey. Further training of clinicians, easier access of patients to specialist multidisciplinary centres and the publication of practice guidelines may help improve the management of this condition in Europe.

Recent developments in the medical treatment of thyroid eye disease.

No real new treatment has been developed in the last decade for thyroid eye disease (TED). Glucocorticoids (GC), orbital radiotherapy (OR) or a combination of both, are most frequently used in the treatment of TED for the iv immunosuppressive effects. However, we now have novel information regarding the when and how corticosteroids should be used. In general, the iv route of GC administration is preferable to the oral use. iv GC should be used at much lower doses than previously (4.5 to 6 g cumulative dose), possibly with a small dose of oral prednisone (or equivalent) in the interpulse period and for a few weeks after completion of iv treatment. Careful assessment of patients before treatment for identification of possible risk factors of liver toxicity is mandatory. Finally, monitoring of patients, particularly for liver function, is warranted during and after treatment. Although OR's effectiveness was disputed by a study few years ago, more recent studies have reconfirmed its beneficial role in TED and shown that it still has a positive role to play in patients with active TED. Finally, although Somatostatin-analogs (SM-as) gave the impression some years ago that might represent an effective weapon for TED management and initial, mostly uncontrolled and non-randomized trials with small number of patients supported this notion, newer randomized, double-blind studies with larger number of patients have not confirmed the first optimistic results. The question after that is if SM-as should be considered as a rubber bullet in the treatment of TED and we have to forget about them. The answer should be "no yet," especially in the light that the role of SM-as may be revitalized by the use of analogs with higher affinity for all somatostatin receptors subtypes. Such analogs are now available and under investigation in different diseases with very promising results.

Endoscopic endonasal assistance with Jones lacrimal bypass tubes.

Rigid nasal endoscopy is a reliable technique that can be used to assist in the preoperative nasal evaluation, operative tube positioning, and management after surgery. Postoperative function can be evaluated by using a passive dye test (FEDT) viewed directly, and minor interventions carried out without the need to remove the tube or do excessive probing. Endonasal endoscopy facilitates the maintenance of tube function with minimal manipulation and patient discomfort, and is fast and efficient. Its use should help improve tube retention and function. A detailed study over a number of years is necessary to provide convincing evidence for improving clinical standards. Lester T Jones wrote: The postoperative care of such a patient (having a glass bypass tube) should be in the hands of a physician who is willing to look into the nose, as inspection of the length and position of glass tube is most important. Endoscopic endonasal assistance helps the ophthalmologist to fulfill his criteria.

A comparative study of two procedures for repair of involutional lower lid entropion.

OBJECTIVE: The study compares the use of Jones' retractor plication and the Wies procedure as a primary procedure for the repair of involutional lower lid entropion in the absence of horizontal lid shortening. DESIGN: Retrospective case series comparison. PARTICIPANTS: One hundred two cases with at least 6 months follow-up after primary surgery for involutional lower lid entropion performed between 1993 and 1996. INTERVENTIONS: Two groups were compared: Jones' retractor plication was performed in one group and the Wies procedure in the other; neither group had horizontal shortening of the lower eyelid. MAIN OUTCOME MEASURES: The rates of cure, recurrence, and overcorrection of the lower lid entropion. RESULTS: Jones' retractor plication was performed in 37 (36%) patients and the Wies procedure in 65 (64%). Two of the 37 (5%) Jones cases had recurrent entropion develop, both at 31 months after surgery, compared with 1 1 of 65 (17%) recurrences after the Wies procedure (P = 0.81); recurrence after Wies procedure was earlier, at a median of 6 months after surgery. There were 20 of 65 (31 %) overcorrections after the Wies procedure and 4 of 37 (11 %) after the Jones procedure (P < 0.02); one quarter of each group required secondary repair of the overcorrection (5 of 20 after failed Wies procedure; 25% after failed Jones procedure). Overall, there were 6 of 37 (16%) unsatisfactory results after the Jones procedure in contrast to 31 of 65 (48%) after the Wies procedure (P < 0.001). CONCLUSIONS: These data provide strong evidence (P < 0.001) that, in the absence of horizontal shortening of the lower eyelid, a successful outcome is more likely after Jones retractor plication than after the Wies procedure.