Antimetabolites as an adjunct to dacryocystorhinostomy for nasolacrimal duct obstruction.

BACKGROUND: Nasolacrimal duct obstruction (NLDO) is a condition that results in the overflow of tears (epiphora) or infection of the nasolacrimal sac (dacryocystitis). The etiology of acquired NLDO is multifactorial and is not fully understood. Dacryocystorhinostomy (DCR) is the surgical correction of NLDO, which aims to establish a new drainage pathway between the lacrimal sac and the nose. The success of DCR is variable; the most common cause of failure is fibrosis and stenosis of the surgical ostium. Antimetabolites such as mitomycin-C (MMC) and 5-fluorouracil (5-FU) have been shown to be safe and effective in reducing fibrosis and improving clinical outcomes in other ophthalmic surgery settings (e.g. glaucoma and cornea surgery). Application of antimetabolites at the time of DCR has been studied, but the utility of these treatments remains uncertain. OBJECTIVES: Primary objective: To determine if adjuvant treatment with antimetabolites improves functional success in the setting of DCR compared to DCR alone. Secondary objectives: To determine if anatomic success of DCR is increased with the use of antimetabolites, and if the surgical ostium is larger in participants treated with antimetabolites. SEARCH METHODS: We searched the Cochrane Register for Controlled Trials (CENTRAL) (which contains the Cochrane Eye and Vision Trials Register) (2019, Issue 9), Ovid MEDLINE, Embase.com, PubMed, LILACS (Latin American and Caribbean Health Sciences Literature database), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic searches. We last searched the electronic databases on 6 September 2019. SELECTION CRITERIA: We only included randomized controlled trials. Eligible studies were those that compared the administration of antimetabolites of any dose and concentration versus placebo or another active treatment in participants with NLDO undergoing primary DCR and reoperation. We only included studies that had enrolled adults 18 years or older. We also included studies that used silicone intubation as part of the DCR procedure. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently screened the search results, assessed risk of bias, and extracted data from the included studies using an electronic data collection form. MAIN RESULTS: We included 31 studies in the review, of which 23 (1309 participants) provided data relating to our primary and secondary outcomes. Many of the 23 studies evaluated functional success, while others also assessed our secondary outcomes of anatomic success or ostium size, or both. Study characteristics Participant characteristics varied across studies, with the age of participants ranging from 30 to 70 years. Participants were predominantly women. These demographics correspond to those most frequently affected by nasolacrimal duct obstruction. Almost all of the studies utilized MMC as the antimetabolite, with only one using 5-FU. We assessed most trials as at unclear risk of bias for most domains. Conflicts of interest were not frequently reported, although the antimetabolites used are generic medications, and studies were not likely to be conducted for financial interest. Findings Twenty studies provided data on the primary outcome of functional success, of which 7 (356 participants) provided data at 6 months and 14 (909 participants) provided data beyond 6 months. At six months, the results showed no evidence of effect of antimetabolite on functional success (risk ratio (RR) 1.12, 95% confidence interval (CI) 0.98 to 1.29; low-certainty evidence). Beyond six months, the results favored the antimetabolite group (RR 1.15, 95% CI 1.07 to 1.25; moderate-certainty evidence). Fourteen studies reported data on the secondary outcome of anatomic success, of which 4 (306 participants) reported data at 6 months and 12 (831 participants) provided data beyond 6 months. Results at six months showed no evidence of effect of antimetabolite on anatomic success (RR 1.02, 95% CI 0.95 to 1.11; low-certainty evidence). Beyond six months, participants in the antimetabolite group were more likely to achieve anatomic success than those receiving DCR alone (RR 1.09, 95% CI 1.04 to 1.15; moderate-certainty evidence). At six months and beyond six months follow-up, two studies reported mean change in ostium size. We did not conduct meta-analysis for the various follow-up periods due to clinical, methodological, and statistical heterogeneity. However, point estimates from these studies at six months consistently favored participants in the antimetabolite group (low-certainty evidence). Beyond six months, while point estimates from one study favored participants in the antimetabolite group, estimates from another study showed no evidence of a difference between the two groups. The certainty of evidence at both time points was low. Adverse events Adverse events were rare. One study reported that one participant in the MMC group experienced delayed wound healing. Other studies reported no significant adverse events related to the application of antimetabolites. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that application of antimetabolites at the time of DCR increases functional and anatomic success of DCR when patients are followed for more than six months after surgery, but no evidence of a difference at six months, low-certainty of evidence. There is low-certainty evidence that combining antimetabolite with DCR increases the size of the lacrimal ostium at six months. However, beyond six months, the evidence remain uncertain. Adverse effects of the application of antimetabolites were minimal.

Avoiding the Hughes flap in lower eyelid reconstruction.

PURPOSE OF REVIEW: To review current surgical practices of lower eyelid reconstruction with a focus on recent studies. RECENT FINDINGS: Combination techniques and new flap techniques offer efficacy comparable with existing reconstructive approaches, with the advantage of less local trauma. Inappropriate handling of posterior lamellar grafts, such as kerfing, may predispose to graft failures. Modified Hughes procedure is a favorable choice for large lower eyelid reconstruction; however, it requires temporary eye closure. Other surgical options have been developed to achieve a 1-stage procedure without the need of eye closure. These include the Smith-modified Kuhnt-Szymanowski procedure and the use of flaps. For posterior lamellar grafts, both nasal septal and ear cartilage donor tissue produce esthetically and functionally satisfactory outcomes and comparable efficacy. However, the ear cartilage carries a lower risk of donor site complications. SUMMARY: Lower eyelid reconstruction remains a challenge, especially for large or near total defects. Recent studies have explored modifications and alternatives to the conventional Hughes flap. New surgical procedures give surgeons more options. Taking into account the growing spectrum of reconstructive techniques, an individualized approach may facilitate better functional and esthetic outcomes.

Use of anti-vascular endothelial growth factor in the management of pterygium.

The rising success of anti-vascular endothelial growth factor (VEGF) therapies in ocular disease has stimulated the use of such treatments in the surgical management of pterygium. We reviewed the literature to better understand the safety and efficacy of the adjunctive role of anti-VEGF treatments for pterygium excision. Without surgery, anti-VEGF alone may favourably alter symptoms and vascularity, but does not cause pterygium regression. Some evidence supports the use of anti-VEGF as an adjuvant therapy to surgery, especially when using a higher dose and a more frequent dosing regimen. Overall, anti-VEGF is generally safe and well tolerated in patients with pterygium. Currently, the evidence does not conclusively support the use of anti-VEGF in pterygium surgery. However, further research may guide unanswered questions regarding the interaction between VEGF and other factors responsible for pterygium growth. In addition, the optimal route and dosage of anti-VEGF administration is not yet known.

Involutional entropion: risk factors and surgical remedies.

PURPOSE OF REVIEW: To review current surgical practices for the repair of lower eyelid involutional entropion with a focus on recent studies. RECENT FINDINGS: A shorter axial length, which may be interrelated with exophthalmometry, correlates with involutional entropion. Although it is known Asian eyelids more frequently develop involutional entropion, there is greater awareness of customized surgical approaches. Minimally invasive techniques for strengthening the action of lower eyelid retractors, such as everting sutures and transconjunctival approaches, continue to be refined and studied. Such surgery is efficacious in patients who do not have horizontal laxity. However, there is consistent evidence that in the presence of laxity the recurrence rate is higher if the eyelid is not horizontally tightened. SUMMARY: By knowing of the demographics and factors associated with involutional entropion, clinicians can have better understanding of the condition and the patients most at risk. There is not sufficient evidence to determine whether a short axial length is an independent-risk factor for entropion. Advances in surgical technique have led to continued interest in minimally invasive approaches. Precision in addressing individual patients' underlying anatomic abnormalities is important.

Safety and Efficacy of Lacrimal Drainage System Plugs for Dry Eye Syndrome: A Report by the American Academy of Ophthalmology.

OBJECTIVE: To review the published literature assessing the efficacy and safety of lacrimal drainage system plug insertion for dry eye in adults. METHODS: Literature searches of the PubMed and Cochrane Library databases were last conducted on March 9, 2015, without date restrictions and were limited to English language abstracts. The searches retrieved 309 unique citations. The primary authors reviewed the titles and abstracts. Inclusion criteria specified reports that provided original data on plugs for the treatment of dry eyes in at least 25 patients. Fifty-three studies of potential relevance were assigned to full-text review. The 27 studies that met the inclusion criteria underwent data abstraction by the panels. Abstracted data included study characteristics, patient characteristics, plug type, insertion technique, treatment response, and safety information. All studies were observational and rated by a methodologist as level II or III evidence. RESULTS: The plugs included punctal, intracanalicular, and dissolving types. Fifteen studies reported metrics of improvement in dry eye symptoms, ocular-surface status, artificial tear use, contact lens comfort, and tear break-up time. Twenty-five studies included safety data. Plug placement resulted in ≥50% improvement of symptoms, improvement in ocular-surface health, reduction in artificial tear use, and improved contact lens comfort in patients with dry eye. Serious complications from plugs were infrequent. Plug loss was the most commonly reported problem with punctal plugs, occurring on average in 40% of patients. Overall, among all plug types, approximately 9% of patients experienced epiphora and 10% required removal because of irritation from the plugs. Canaliculitis was the most commonly reported problem for intracanalicular plugs and occurred in approximately 8% of patients. Other complications were reported in less than 4% of patients on average and included tearing, discomfort, pyogenic granuloma, and dacryocystitis. CONCLUSIONS: On the basis of level II and III evidence in these studies, plugs improve the signs and symptoms of moderate dry eye that are not improved with topical lubrication, and they are well tolerated. There are no level I studies that describe the efficacy or safety of lacrimal drainage system plugs.

Eyelid myeloid sarcoma: ominous presentation of acute myelogenous leukemia.

A 19 year-old African American man presented to our clinic for a second opinion about a right upper eyelid mass which had been recalcitrant to treatment for nonspecific orbital inflammation by an outside facility. Examination for systemic causes of the patients eyelid lesion led to a diagnosis of acute myelogenous leukemia (AML) FAB subtype M1. A subsequent biopsy of the eyelid tumor confirmed the diagnosis of a myeloid sarcoma. The patient succumbed to complications from his leukemia within 13 months of presentation. This case report is the first, to our knowledge, of an eyelid myeloid sarcoma as the presenting sign of AML and demonstrates the poor prognosis of this lesion.

Age-Related True Exfoliation of the Lens Capsule: Phacoemulsification Surgery Results.

Historically associated with glassblowers, true exfoliation of the crystalline lens involves a splitting or delamination of the capsule. We reviewed the phacoemulsification records of a single surgeon for patients with true exfoliation of the lens capsule. The incidence in our series was 2.2% (6 in 278 cases). The average age was 85.0 years. All patients had successful phacoemulsification outcomes, which may have been due to accurate recognition of the condition and appropriate surgical planning. Our findings support the notion that true exfoliation may be more often associated with advanced age rather than infrared radiation.

Evidence-based review of surgical practices in endoscopic endonasal dacryocystorhinostomy for primary acquired nasolacrimal duct obstruction and other new indications.

PURPOSE OF REVIEW: To review the current surgical practices in endoscopic endonasal dacryocystorhinostomy (EN-DCR) from the studies of last 12 months. RECENT FINDINGS: Success rates in EN-DCR now rival those of the conventional external approach. Indications are expanding beyond primary acquired nasolacrimal duct obstruction to include DCR revisions, acute lacrimal sac abscesses, nasolacrimal duct obstructions in patients who have received chemotherapy or radiation, and common canalicular obstructions. There is limited evidence that intubation with silicone stents improves the outcomes. Mitomycin C appears to improve the success rates of EN-DCR, especially revision surgery. Concomitant procedures, such as septoplasty and anterior middle turbinectomy, are sometimes required in primary as well as revision EN-DCR to achieve high success rates. There is increasing evidence that silicone stents are of limited benefit, whereas mucosal flap formation has been of benefit in case series. SUMMARY: With innovations and improvements in the endonasal approach, EN-DCR has become a viable alternative to external DCR for primary acquired nasolacrimal duct obstruction. EN-DCR has the distinct advantages of no surface scar and a lack of damage to the pump mechanism that often occur with external DCR. Recent evidence indicates a comparable success rate to external DCR.

Delayed administration of bone marrow mesenchymal stem cell conditioned medium significantly improves outcome after retinal ischemia in rats.

PURPOSE: Delayed treatment after ischemia is often unsatisfactory. We hypothesized that injection of bone marrow stem cell (BMSC) conditioned medium after ischemia could rescue ischemic retina, and in this study we characterized the functional and histological outcomes and mechanisms of this neuroprotection. METHODS: Retinal ischemia was produced in adult Wistar rats by increasing intraocular pressure for 55 minutes. Conditioned medium (CM) from rat BMSCs or unconditioned medium (uCM) was injected into the vitreous 24 hours after the end of ischemia. Recovery was assessed 7 days after ischemia using electroretinography, at which time we euthanized the animals and then prepared 4-µm-thick paraffin-embedded retinal sections. TUNEL and Western blot were used to identify apoptotic cells and apoptosis-related gene expression 24 hours after injections; that is, 48 hours after ischemia. Protein content in CM versus uCM was studied using tandem mass spectrometry, and bioinformatics methods were used to model protein interactions. RESULTS: Intravitreal injection of CM 24 hours after ischemia significantly improved retinal function and attenuated cell loss in the retinal ganglion cell layer. CM attenuated postischemic apoptosis and apoptosis-related gene expression. By spectral counting, 19 proteins that met stringent identification criteria were increased in the CM compared to uCM; the majority were extracellular matrix proteins that mapped into an interactional network together with other proteins involved in cell growth and adhesion. CONCLUSIONS: By restoring retinal function, attenuating apoptosis, and preventing retinal cell loss after ischemia, CM is a robust means of delayed postischemic intervention. We identified some potential candidate proteins for this effect.

Full-thickness eyelid lesions in sarcoidosis.

Eyelid involvement in sarcoidosis is very rare. A search of the medical literature indicates one previous report of sarcoidosis with destructive eyelid lesions. We describe the case of a 50-year-old woman with severe systemic sarcoidosis, which included her eyelids. To our knowledge, the case presented herein represents the first to show the full-thickness histopathology of destructive eyelid lesions in sarcoidosis.

Proximal tarsal attachments of the levator aponeurosis: implications for blepharoptosis repair.

PURPOSE: To examine the tarsal attachments of the levator aponeurosis. DESIGN: Experimental anatomic study. PARTICIPANTS: Sixteen orbits from 12 fresh frozen white cadavers. METHODS: Eight specimens served as controls. In the remaining 8 specimens from 4 cadavers, the upper eyelid was everted. All specimens then were fixed in formalin. The age, sex, and laterality were recorded in both groups. The eyelid lamellae and tarsal attachments of the levator aponeurosis in particular were examined microscopically. Lamellar and nonlamellar ocular anatomic features and the relationships of the preaponeurotic and postaponeurotic spaces were measured. MAIN OUTCOME MEASURES: Histologic findings of the extent and pattern of the tarsal attachments of the levator aponeurosis in relation to the tarsus and Müller's muscle and of the changes in the lamellae in eyelid eversion. RESULTS: The demographic and baseline anatomic characteristics of both the noneverted control and everted eyelid groups were similar. In comparing everted with noneverted controls, the preaponeurotic space was significantly shorter (6.22 and 10.61 mm, respectively; P = 0.003) and the preaponeurotic-to-postaponeurotic space ratio was halved (0.57 and 1.16, respectively; P = 0.005). Although the distance from the superior tarsal border to Whitnall's ligament increased significantly in everted versus noneverted eyes (14.65 and 11. 03 mm, respectively; P = 0.016), there was no significant difference in the length of postaponeurotic space in the 2 groups (11.07 and 9.69 mm, respectively; P = 0.370). The levator aponeurosis attached to the anterior tarsus in both groups. The proximal point of attachment was the superior border of the tarsal plate, adjacent to the insertion of Müller's muscle tendon. CONCLUSIONS: The deeper aponeurotic fibers and Müller's muscle attach proximally at the superior tarsal border. Upon eyelid eversion, the 2 lamellae move as a unit and the postaponeurotic space remains stable. A proximal tarsal attachment suggests that blepharoptosis procedures that advance an involutional or disinserted levator aponeurosis onto to the superior tarsus approximate that aspect of native anatomic features. In addition, posterior surgical approaches that address Müller's muscle may involve resections in closer proximity to the aponeurosis than previously thought. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Levator palpebrae superioris: an anatomical update.

The levator palpebrae superioris (LPS) muscle is the main retractor of the upper eyelid, responsible for elevating the upper eyelid and maintaining it in an open position. Sound knowledge of its anatomy and adjacent structures is essential for eyelid surgery. Work from researchers and anatomists over the years continue to enrich our understanding in the anatomy of the LPS. In this review, we present an update on the anatomy of the LPS and its surgical implications. Important adnexa such as Whitnall's ligament, intermuscular-transverse ligament and Müller's muscle are also covered.

Functional indications for upper eyelid ptosis and blepharoplasty surgery: a report by the American Academy of Ophthalmology.

OBJECTIVE: To evaluate the functional indications and outcomes for blepharoplasty and blepharoptosis repair by assessing functional preoperative impairment and surgical results. METHODS: Literature searches of the PubMed and Cochrane Library databases were conducted on July 24, 2008, with no age or date restrictions, and they were limited to articles published in English. These searches retrieved 1147 citations; 87 studies were reviewed in full text, and 13 studies met inclusion criteria and were included in the evidence analysis. RESULTS: The 13 studies reported the functional effects or treatment results of simulated ptosis; several types of blepharoptosis repair, including conjunctiva-Müller's muscle resection, frontalis suspension, and external levator resection; and upper eyelid blepharoplasty. CONCLUSIONS: Repair of blepharoptosis and upper eyelid dermatochalasis provides significant improvement in vision, peripheral vision, and quality of life activities. Preoperative indicators of improvement include margin reflex distance 1 (MRD(1)) of 2 mm or less, superior visual field loss of at least 12 degrees or 24%, down-gaze ptosis impairing reading and other close-work activities, a chin-up backward head tilt due to visual axis obscuration, symptoms of discomfort or eye strain due to droopy lids, central visual interference due to upper eyelid position, and patient self-reported functional impairment. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Eyelid eversion for visualisation of the upper eyelid lamellae: an anatomical cadaver study.

Controversy persists in surgical eyelid anatomy despite the routine use of microanatomical examination in modern eyelid research. The aim of our study was to facilitate visualisation of upper eyelid anatomy by optimising the orientation of cadaveric specimens. We studied the anatomy of everted eyelids, providing an excellent histological view of the posterior approach to the eyelid commonly used in surgery. Non-traumatic separation of the eyelid lamellae provides a new view of the eyelid's lamellar nature. Further application of this model may enhance understanding of the multilayered aspect of the levator aponeurosis. The technique may improve intraoperative understanding of critical eyelid anatomy and promote safer and more effective eyelid surgery.

Protein kinase B (Akt) and mitogen-activated protein kinase p38α in retinal ischemic post-conditioning.

In previous studies, it was shown that post-conditioning, a transient period of brief ischemia following prolonged severe ischemia in the retina, could provide significant improvement in post-ischemic recovery, attenuation of cell loss, and decreased apoptosis. However, the mechanisms of post-conditioning in the retina have not been elucidated. We hypothesized that two kinases, mitogen-activated protein kinase p38α and protein kinase B (Akt), were involved in the mechanism of post-conditioning. Ischemia was induced in rat retina in vivo. Recovery after ischemia followed by 8 min of post-conditioning early in the reperfusion period after prolonged ischemia was assessed functionally (electroretinography) and histologically at 7 days after ischemia. We examined the role of p38α and Akt subtypes 1-3 in post-conditioning by intravitreal injection of interfering RNA 6 h prior to ischemia and post-conditioning and compared the results to injection of non-silencing interfering RNA sequence. The blockade of p38α significantly decreased the recovery after ischemia and post-conditioning, and enhanced cell loss and disorganization of the retina. Blockade of Akt1, and to a lesser degree, Akt2, significantly decreased the recovery after ischemia and enhanced cell loss and disorganization. These differences in the effects of blockade of Akt subtypes were not explainable by distribution of Akt subtypes in the retina, which were similar. In conclusion, both p38 and Akt are essential components of the neuroprotection induced by post-ischemic conditioning in the retina.

Delayed post-ischemic conditioning significantly improves the outcome after retinal ischemia.

In previous studies, it was shown that post-conditioning, a transient period of brief ischemia following prolonged severe ischemia in the retina, could provide significant improvement in post-ischemic recovery, attenuation of cell loss, and decreased apoptosis. These studies showed that post-conditioning effectively prevented damage after retinal ischemia when it was instituted early (within 1 h) in the post-ischemic period. While post-ischemic conditioning holds high promise of clinical translation, patients often present late after the onset of retinal ischemia and therefore immediate application of this anti-ischemic maneuver is generally not feasible. In this study, we examined the hypothesis that application of a post-conditioning stimulus at 24 h or greater following the end of prolonged ischemia would decrease the extent of ischemic injury. Ischemia was induced in rat retina in vivo. Recovery after ischemia followed by 5 min of post-conditioning brief ischemia 24 or 48 h after prolonged ischemia was assessed functionally (electroretinography) and histologically at 7 days after ischemia and post-conditioning or sham post-conditioning. We found that the brief ischemic stimulus applied 24, but not 48 h after prolonged ischemia significantly improved functional recovery and decreased histological damage induced by prolonged ischemia. We conclude that within a defined time window, delayed post-ischemic conditioning ameliorated post-ischemic injury in rats. Compared to earlier studies, the present work demonstrates for the first time the novel ability of a significantly delayed ischemic stimulus to provide robust neuroprotection in the retina following ischemia.

Mitogen-activated protein kinase phosphatase-1 (MKP-1) in retinal ischemic preconditioning.

We previously described the phenomenon of retinal ischemic pre-conditioning (IPC) and we have shown the role of various signaling proteins in the protective pathways, including the mitogen-activated protein kinase p38. In this study we examined the role in IPC of mitogen-activated protein kinase phosphatase-1 (MKP-1), which inactivates p38. Ischemia was produced by elevation of intraocular pressure above systolic arterial blood pressure in adult Wistar rats. Preconditioning was produced by transient retinal ischemia for 5 min, 24 h prior to ischemia. Small interfering RNA (siRNA) to MKP-1 or a control non-silencing siRNA, was injected into the vitreous 6 h prior to IPC. Recovery was assessed by electroretinography (ERG) and histology. The a-and b-waves, and oscillatory potentials (OPs), measured before and 1 week after ischemia, were then normalized relative to pre-ischemic baseline, and corrected for diurnal variation in the normal non-ischemic eye. The P2, or post-photoreceptor component of the ERG (which reflects function of the rod bipolar cells in the inner retina), was derived using the Hood-Birch model. MKP-1 was localized in specific retinal cells using immunohistochemistry; levels of mitogen-activated protein kinases were measured using Western blotting. Injection of siRNA to MKP-1 significantly attenuated the protective effect of IPC as reflected by decreased recovery of the electroretinogram a and b-waves and the P2 after ischemia. The injection of siRNA to MKP-1 reduced the number of cells in the retinal ganglion cell and outer nuclear layers after IPC and ischemia. Blockade of MKP-1 by siRNA also increased the activation of p38 at 24 h following IPC. MKP-1 siRNA did not alter the levels of phosphorylated jun N-terminal kinase (JNK) or extracellular signal-regulated kinase (ERK) after IPC. The results suggest the involvement of dual-specificity phosphatase MKP-1 in IPC and that MKP-1 is involved in IPC by regulating levels of activated MAPK p38.

Surgical microanatomy of the müller muscle-conjunctival resection ptosis procedure.

PURPOSE: To assess for alterations in the microscopic anatomy that occur as a result of the Müller muscle-conjunctival resection (MMCR) ptosis procedure and to better understand the mechanisms by which MMCR elevates the eyelid. METHODS: Sixteen orbits from 8 fresh frozen Caucasian cadaver heads, ranging from 38 to 100 years of age were used. For each head, MMCR was performed on one side. The contralateral, unoperated orbit served as an anatomic control. Each exenterated orbital contents and excised MMCR specimen was evaluated. The histopathology of the eyelids and MMCR specimens were studied microscopically by staining with hematoxylin-eosin, elastic, and Verhoeff-Masson trichrome. RESULTS: Müller muscle and conjunctiva were present in all 8 of the excised MMCR specimens. Elastic fibers consistent with Müller muscle tendon or among the smooth muscle fibers were seen within all excised MMCR specimens. The levator aponeurosis was intact in 8 of 8 operated eyelids; however, the aponeurosis was plicated in all. The accessory lacrimal gland tissues were intact in all of the operated and unoperated eyelids. CONCLUSIONS: MMCR works by shortening the posterior lamella, which results in advancement of the levator palpebrae superioris muscle and plication of the levator aponeurosis. Plication of the levator aponeurosis likely contributes to the increased volumetric effect seen clinically after MMCR. Phenylephrine testing can help in fine-tuning the amount of resection, but given the mechanism of action of MMCR, adequate levator muscle function remains a critical factor in the success of the surgery. Moreover, MMCR preserves accessory lacrimal gland tissues.

1 alpha-Hydroxyvitamin D2 inhibits growth of human neuroblastoma.

Neuroblastoma is the most common extracranial solid tumor in childhood. The poor outcomes of patients with high-risk neuroblastoma have encouraged the search for new therapies. In the current study, the effect of the vitamin D analog 1alpha-hydroxyvitamin D2 (1alpha-OH-D2, doxercalciferol) was assessed in a mouse xenograft model of human neuroblastoma. Vitamin D receptor (VDR) expression levels in seven neuroblastoma cell lines were compared using real-time PCR. SK-N-AS cells, which express relatively high levels of VDR, were injected into the flanks of 60 mice. The mice were treated daily via oral gavage for 5 weeks with vehicle (control), 0.15 microg, or 0.3 microg of 1alpha-OH-D2. The animals were then euthanized, and tumors, sera, and kidneys were collected and analyzed. End tumor volumes were significantly smaller in both the 0.15 microg group (712.07 mm3, P = 0.0121) and 0.3 microg group (772.97 mm3, P = 0.0209) when compared to controls (1,681.75 mm3). In terms of toxicity, serum calcium levels were increased but mortality was minimal in both treatment groups. These results were similar to those previously described in the transgenic (LHbeta-Tag) and human xenograft (Y-79) models of retinoblastoma, a related tumor. In vitro cell viability studies of SK-N-AS and NGP cells, which represent two major human neuroblastoma subtypes that differ in their genetic abnormalities as well as their VDR expression levels, show that both are sensitive to calcitriol, the active metabolite of vitamin D3. In conclusion, the present study shows that 1alpha-OH-D2 can inhibit human neuroblastoma growth in vivo with relatively low toxicity. The safety of 1alpha-OH-D2 has been extensively studied; the drug is FDA-approved for the treatment of adult kidney patients, and Phase I/II trials have been conducted in adult oncology patients. There should not be major obstacles to starting Phase I and II clinical trials with this drug in pediatric patients with high-risk neuroblastoma.