Durable response to pembrolizumab in hepatic metastasis from colonic carcinoma with Lynch syndrome: a case report.

Pembrolizumab and other immunotherapies have become central in treating metastatic colon cancer, particularly effective in patients with mismatch repair deficiencies. We report a case involving a man who initially underwent radical surgery for sigmoid colon cancer on April 27, 2011, followed by hepatic tumor resection on September 21, 2017. Post-surgery, he received eight cycles of adjuvant chemotherapy with the CAPEOX regimen and was regularly monitored through CT and MRI scans. On August 24, 2022, liver metastases were detected, and he was diagnosed with Lynch syndrome (LS) due to germline mutation in the MSH2 and EPCAM genes. He commenced treatment with 200mg of pembrolizumab intravenously every three weeks on September 2, 2022, and demonstrated a sustained response. However, after 17 cycles, he developed a treatment related adverse event (TRAE) of pancreatic endocrine dysfunction, leading to type 1 diabetes, managed with subcutaneous insulin injections. After 30 cycles of treatment, no evidence of disease was observed. This case underscores the significant clinical benefits of first-line pembrolizumab in managing hepatic metastasis in colonic carcinoma associated with LS, despite the occurrence of TRAEs. It raises critical questions regarding the optimal duration of immunotherapy following a complete or partial response and whether treatment should be discontinued upon the emergency of TRAEs. Continued research and forthcoming clinical trials with checkpoint inhibitors are expected to refine treatment protocols for LS-associated carcinoma.

Clinical efficacy of EUS-guided celiac plexus neurolysis versus EUS-guided celiac ganglion irradiation with iodine-125 seeds for pain relief in advanced pancreatic cancer: A long-term retrospective study.

Background and Objective: To compare the efficacy of EUS-guided celiac plexus neurolysis (CPN) and celiac plexus irradiation with iodine-125 (125I) seeds with absolute ethanol for relieving pain in patients with advanced pancreatic cancer. Methods: We retrospectively analyzed data of 81 patients with advanced pancreatic cancer who underwent EUS-CPN or EUS-125I implantation between January 2017 and December 2020. Postoperative pain was assessed using visual analog scale (VAS) scores; self-assessments of quality of life and the median survival time were compared between the 2 groups. Results: EUS-CPN and 125I implantation were performed in 43 and 38 patients, respectively. Postoperative VAS scores were significantly lower than the preoperative levels in both groups. One week after the operation, 26 patients (60.5%) in the EUS-CPN group achieved partial pain relief, whereas no patients in the EUS-125I seed group experienced pain relief. However, after 4 weeks postoperatively, VAS scores had decreased, and the rate of partial pain relief was higher for EUS-125I seeds than for EUS-CPN. Self-assessments of quality of life were similar in both groups during the first 1 month after the procedure. Conclusions: Both EUS-CPN and EUS-125I seeds can safely and effectively relieve pain in patients with advanced pancreatic cancer. Although EUS-125I seeds take additional time to show effects, the extent and duration of pain relief are better compared with CPN, and interestingly, the median survival time was different.

Silicone oil as a corneal lubricant to reduce corneal edema and improve visualization during vitrectomy.

AIM: To evaluate the efficacy and safety of silicone oil (SO) as a corneal lubricant to improve visualization during vitrectomy. METHODS: Patients who underwent vitreoretinal surgery were divided into two groups. Group 1 was operated on with initial SO (Oxane 5700) as a corneal lubricant. Group 2 was operated on with initial lactated ringer's solution (LRS) and then replaced with SO as required. Fundus clarity was scored during the surgery. Fluorescein staining was performed to determine the damage to corneal epithelium. RESULTS: Totally 114 eyes of 114 patients were included. Single SO use maintained a clear cornea and provided excellent visualization of surgical image. In group 1, the fundus clarity was grade 3 in 41/45 eyes and grade 2 in 4/45 eyes. In group 2, corneal edema frequently occurred after initial LRS use. The fundus clarity was grade 3 in 19/69 eyes, 2 in 37/69 eyes and 1 in 13/69 eyes (P<0.05). SO was applied in 29 eyes of initial LRS use with subsequent corneal edema, which eliminated the corneal edema in 26 eyes. Corneal fluorescein staining score in group 1 was 0 in 28 eyes, 1 in 11 eyes and 2 in 6 eyes, and 40, 20 and 9, respectively, in group 2 (all P>0.05). CONCLUSION: The use of SO as a corneal lubricant is effective and safe for preserving and improving corneal clarity and providing clear surgical field during vitrectomy.

Long-term follow-up of endoscopic papillectomy and the value of preventive pancreatic stent placement (with videos).

Background: Early-stage ampullary adenomas have only been reported in a small case series on endoscopic management. Hence, this study aimed to evaluate the long-term outcomes of early ampullary adenoma with endoscopic management and identify the risk factors for acute pancreatitis after endoscopic papillectomy (EP). Methods: In this study, 115 patients who underwent EP at Changhai Hospital (Shanghai, China) between January 2012 and December 2018 were retrospectively analysed. Endoscopy was performed at 1, 3, 6, and 12 months after EP. Data were statistically analysed using the t-test or the Mann-Whitney U test. Results: A total of 107 patients were included in this study and the follow-up period was 75 ± 43 months. The average age of the 107 patients was 54.6 years and the average tumor size was 17 mm. The average age of the patients (53.7 ± 10.7 years vs 55.2 ± 10.5 years, P = 0.482), minimum tumor size (13 vs 19 mm, P = 0.063), and complete resection rate (84.78% vs 85.25%, P = 0.947) did not differ significantly between the stent placement and non-stent placement groups. Post-EP acute pancreatitis rates in the non-stent placement and stent placement groups were 11.48% and 4.35%, respectively. The risk of post-EP acute pancreatitis was significantly associated with the preoperative carcinoembryonic antigen level in univariate analysis, but not in multivariate analysis. The risk of post-EP acute pancreatitis was not significantly associated with the placement of the pancreatic stent in either univariate or multivariate analysis. Moreover, delayed proximal pancreatic duct stenosis was not noted in either group during long-term follow-up. Conclusions: EP is a satisfactory option for treating adenomas of the ampulla of the duodenum.

Early surgery improves peripheral motor axonal dysfunction in acute traumatic central cord syndrome: A prospective cohort study.

OBJECTIVE: To investigate the impact of early vs. delayed surgical decompression on peripheral motor axonal dysfunction following acute traumatic central cord syndrome (ATCCS). METHODS: Both axonal excitability testing and motor unit number estimation (MUNE) were performed in 30 ATCCS patients (early- vs. delayed-surgical treatment: 12 vs. 18) before operation and 28 healthy subjects. Axonal excitability testing was repeated 3-5 days and 1-year after operation, and MUNE was re-evaluated 1-year after operation. RESULTS: Preoperatively, an obvious modification in membrane potentials was observed in ATCCS patients that mostly coincided with depolarization-like features, and MUNE further revealed reduced motor units in tested muscles (P < 0.05). Unlike delayed-surgical cases, early-surgical cases showed recoveries of most measurements of axonal excitabilities soon after operation (P < 0.05). Postoperative one-year follow-up demonstrated that greater motor unit numbers in tested muscles were obtained in early-surgical cases than in delayed-surgical cases (P < 0.05). CONCLUSIONS: ATCCS has adverse downstream effects on peripheral nervous system, even in the early stage of ATCCS. Early surgical treatment can ameliorate both excitability abnormalities and motor unit loss in distal motor axons. SIGNIFICANCE: Optimizing axonal excitability in the early phases of ATCCS may alleviate peripheral nerve injury secondary to lesions of upper motor neuron and improve clinical outcomes.

Modified deep anterior lamellar dissection for corneal opacity during vitrectomy: case reports.

BACKGROUND: To introduce a modified deep anterior lamellar dissection technique to improve visibility during surgery for vitreoretinal diseases with coexisting corneal opacity. CASE PRESENTATION: Two patients with retinal detachment and coexisting corneal blood staining or corneal decompensation underwent modified deep anterior lamellar dissections followed by vitrectomy. The modified deep anterior lamellar dissection techniques, unlike the dissection and removal of corneal lamellar in a typical deep anterior lamellar keratoplasty, included the creation and preservation of a deep lamellar corneal flap, the retroillumination to visualize and easily remove the remaining opaque stroma on the Descemet membrane, and the big air bubble technique in the eye with endothelial decompensation. The patient's own cornea flap was sutured back after vitrectomy was done. The modified dissection techniques provided adequate fundus view during vitrectomy while removing as less corneal tissue as possible and decreasing the surgical complications and the requirement of a fresh cornea. Postoperatively, in case 1, the corneal blood staining was gradually absorbed and the vision improved from light perception to counting fingers. In case 2, even though the cornea remained cloudy and the vision was poor, the cornea endothelial decompensation was stable and asymptomatic. Both retinas were attached after silicone oil removal at 6-month follow-up. CONCLUSIONS: This modified and limited deep anterior lamellar corneal dissection procedure appears to be a useful alternative to penetrating keratoplasty, ophthalmic endoscope and temporary keratoprosthesis during the vitrectomy with coexisting corneal opacity.

microRNA profiling in the aqueous humor of highly myopic eyes using next generation sequencing.

PURPOSE: To characterize microRNAs (miRNAs) and their possible roles in high myopia by using next generation sequencing. METHODS: Aqueous humor samples were obtained from 25 highly myopic eyes and 25 cataract eyes at the onset of surgery. miRNA next generation sequencing and bioinformatics analyses were performed using RNA extracted from 30 samples. The remaining 20 samples were used for quantitative polymerase chain reaction validation of sequencing results. RESULTS: A total of 341 microRNAs were detected in the aqueous humor samples of highly myopic eyes; 201 miRNAs were detected in the aqueous humor samples of cataractous control eyes. A total of 249 mature miRNAs and 17 novel miRNAs were differentially expressed during myopia. Possible pathways regulated by these aberrantly expressed miRNAs included the TNF, MAPK, PI3K-Akt, and HIF-1 signaling pathways. The relative expression patterns of hsa-let-7i-5p, hsa-miR-127-3p, and hsa-miR-98-5p were confirmed by quantitative polymerase chain reaction. CONCLUSIONS: The current study provided an overall view of miRNA profiling in the aqueous humor of highly myopic eyes. These profiles may be associated with myopia pathogenesis, and are potential biomarkers.

Scaffold Hopping-Driven Optimization of 4-(Quinazolin-4-yl)-3,4-dihydroquinoxalin-2(1H)-ones as Novel Tubulin Inhibitors.

Scaffold hopping-driven lead optimizations were performed based on our prior lead 7-methoxy-4-(2-methylquinazolin-4-yl)-3,4-dihydroquinoxalin-2(1H)-one (2a) by C-ring expansion and isometric replacement of the A/B-ring, successively, aimed at finding new potential alternative drug candidates with different scaffold(s), high antitumor activity, and other improved properties to replace prior, once promising drug candidates that failed in further studies. Two series of new compounds 7 (a-d) and 13 (a-j) were synthesized and evaluated for antitumor activity, leading to the discovery of three highly potent compounds 13c, 13d, and 13e with different scaffolds. They exhibited similar high antitumor activity with single digital low nanomolar GI50 values (4.6-9.6 nM) in cellular assays, comparable to lead 2a, clinical drug candidate CA-4, and paclitaxel in the same assays. Further biological evaluations identified new active compounds as tubulin polymerization inhibitors targeting the colchicine binding site. Moreover, 13d showed better aqueous solubility than 2a and a similar log P value.

AUTOLOGOUS BLOOD CLOT COVERING INSTEAD OF GAS TAMPONADE FOR MACULAR HOLES.

PURPOSE: This study evaluates the efficacy and usefulness of vitrectomy with internal limiting membrane peeling and autologous blood clot covering without gas tamponade in the treatment of macular holes (MHs). METHODS: All patients with a full-thickness MH with a minimum diameter of <600 µm and a base diameter of <1,200 µm underwent pars plana vitrectomy and internal limiting membrane peeling with autologous blood covering the MH at the end of the surgery. No fluid-air exchange or gas tamponade was performed. Postoperatively, all patients were instructed to adopt supine position overnight and thereafter any comfortable posture. RESULTS: A total of 18 eyes of 18 consecutive patients were included. The mean age of the patients (12 women and 6 men) was 59.06 ± 14.31 years (range, 21-81 years). The MHs composed of 13 idiopathic MHs, 2 MHs with high myopia (axial length > 26.5 mm), 2 traumatic MHs, and 1 MH associated with diabetic macular edema. Among them were five large MHs (minimum diameter > 400 µm). Complete MH closure was achieved in all eyes at the end of the follow-up period (range, 3-14 months). Visual acuity was significantly improved from preoperative 0.89 ± 0.41 logarithm of the minimum angle of resolution (20/155 Snellen) to 0.42 ± 0.33 logarithm of the minimum angle of resolution (20/53 Snellen) at the final visit (P < 0.001). CONCLUSION: The novel surgical protocol using vitrectomy, internal limiting membrane peeling, and autologous blood clot covering at the end of the MH surgery with limited diameters achieved highly effective closure and visual improvement and eliminated the gas tamponade and thus the associated adverse effects and the need for postoperative face-down positioning.

Biochemical Characterization of a Multifunctional Mononuclear Nonheme Iron Enzyme (PtlD) in Neopentalenoketolactone Biosynthesis.

Pentalenolactone is a microbial sesquiterpenoid with antibiotic activity. Its biosynthetic pathway was elucidated by a combination of genetic and biochemical characterizations of all genes involved. For the related neopentalenoketolactone biosynthetic gene cluster from Streptomyces avermitilis, an α-ketoglutarate-dependent mononuclear nonheme iron enzyme, PtlD, was proposed to catalyze both desaturation and olefin epoxidation reactions. Yet, these activities remained to be validated by in vitro biochemical evidence. In this report, we demonstrated that PtlD has multiple activities, including hydroxylation, desaturation, and epoxidation, and confirmed the presence of the elusive epoxide intermediate in a neopentalenoketolactone pathway.

Motor unit number index (MUNIX) in the quantitative assessment of severity and surgical outcome in cervical spondylotic amyotrophy.

OBJECTIVE: To assess the feasibility of motor unit number index (MUNIX) in the quantitative assessment of the cervical spondylotic amyotrophy (CSA). METHODS: MUNIX was recorded bilaterally on the abductor pollicis brevis, abductor digiti minimi, biceps brachii and middle deltoid in 41 normal controls and 47 patients with CSA (distal-type to proximal-type ratio: 25 to 22). Additionally, patients were assessed on handgrip strength (HGS), the disabilities of arm, shoulder and hand (DASH) and Medical Research Council (MRC) scales. These examinations were re-evaluated approximately 18 months after surgery in 37 of these CSA patients. RESULTS: MUNIX values were noticeably lower in the mainly affected muscles of CSA patients than those in controls (P < 0.05), and 49.0% (51/104) of the tested muscles with abnormal MUNIX measurements showed normal muscle strength. Significant correlations between MUNIX measurements and both DASH and MRC scores were observed in both CSA patient groups (P < 0.05). Postoperative longitudinal follow-up analysis identified significant increase in motor unit number in both CSA patient groups within approximately 18 months (P < 0.05), with or without improved measures of motor function. CONCLUSIONS: A significant reduction in MUNIX values related to motor impairment was observed in CSA patients, even in the subclinical stage. Compared to measures of motor function, the MUNIX measurements in the patients with CSA improved more noticeably after surgical intervention. SIGNIFICANCE: MUNIX may serve as an available supplementary test to quantitatively evaluate the motor dysfunction in CSA and to track its progression, that is complementary to conventional electromyography.

Mechanistic studies of DepR in regulating FK228 biosynthesis in Chromobacterium violaceum no. 968.

DepR, a LysR-type transcriptional regulator encoded by the last gene of the putative min operon (orf21-20-19-depR) located at the downstream region of the anticancer agent FK228 biosynthetic gene cluster in Chromobacterium violaceum No. 968, positively regulates the biosynthesis of FK228. In this work, the mechanism underlining this positive regulation was probed by multiple approaches. Electrophoretic mobility shift assay (EMSA) and DNase I footprinting assay (DIFA) identified a conserved 35-nt DNA segment in the orf21-orf22 intergenic region where the purified recombinant DepR binds to. Quantitative reverse transcription PCR (RT-qPCR) and green fluorescent protein (GFP) promoter probe assays established that transcription of phasin gene orf22 increases in the depR deletion mutant of C. violaceum (CvΔdepR) compared to the wild-type strain. FK228 production in the orf22-overexpressed strain C. violaceum was reduced compared with the wild-type strain. DepR has two conserved cysteine residues C199 and C208 presumed to form a disulfide bridge upon sensing oxidative stress. C199X point mutations that locked DepR in a reduced conformation decreased the DNA-binding affinity of DepR; T232A or R278A mutation also had a negative impact on DNA binding of DepR. Complementation of CvΔdepR with any of those versions of depR carrying a single codon mutation was not able to restore FK228 production to the level of wild-type strain. All evidences collectively suggested that DepR positively regulates the biosynthesis of FK228 through indirect metabolic networking.

Treatment of Myopic Foveoschisis with Air Versus Perfluoropropane: A Retrospective Study.

BACKGROUND The aim of this study was to compare the efficacy of air and perfluoropropane (C3F8) combined with vitrectomy to treat myopic foveoschisis (MF). MATERIAL AND METHODS A retrospective comparison of a consecutive series of surgical patients was performed. Ninety-seven eyes of 91 patients with MF were assigned to undergo 23G vitrectomy. After internal limiting membrane (ILM) peeling, the vitreous cavity was filled with air in 48 eyes of 45 patients (Air Group). Fluid-air exchange was performed in 49 eyes of 46 patients (C3F8 Group) followed by an injection of 14% C3F8. Patients were evaluated using best-corrected visual acuity (BCVA) and optical coherence tomography. RESULTS Preoperatively, there was no significant difference in clinical features between the groups. After surgery, BCVA was markedly improved and the foveoschisis height was reduced in both groups compared with baseline (P<0.01), but the difference between the groups was not significant (P>0.05). No significant differences were noted in BCVA improvement and retinal restoration (P=0.33 and 0.39, respectively) in the mild and moderate subgroups (foveoschisis height ≤400 µm) between the tamponades. However, in the severe group (foveoschisis height >400 µm), C3F8 had a more favorable cure rate and foveoschisis height reduction improvement compared with air (P=0.04 and 0.04, respectively) at the last visit. CONCLUSIONS Vitrectomy combined with ILM peeling is effective in the treatment of myopic foveoschisis, and the choice of tamponade depends on the severity of foveoschisis. Air can be used for patients with a foveoschisis height ≤400 µm, but C3F8 is more effective for patients with a foveoschisis height >400 µm.

Regulation of Matrix Metalloproteinase-2 Secretion from Scleral Fibroblasts and Retinal Pigment Epithelial Cells by miR-29a.

PURPOSE: To identify an effective method to prevent myopia progression by characterizing the regulation of matrix metalloproteinase- (MMP-) 2 expression and its secretion from scleral fibroblasts and retinal pigment epithelium (RPE) cells by miR-29a. METHODS: The effects of miR-29a on the growth of scleral fibroblasts and RPE cells were assessed using the cell counting kit-8. The changes in MMP-2 mRNA levels in scleral fibroblasts and RPE cells after transfection with miR-29a mimics or inhibitor were measured by quantitative PCR. Enzyme-linked immunosorbent assays were used to determine the changes in MMP-2 secretion from scleral fibroblasts and RPE cells after transfection with miR-29a mimics or inhibitor. RESULTS: The miR-29a mimics or inhibitor did not significantly alter the growth of scleral fibroblasts or RPE cells at 24, 48, or 72 hours after transfection. MMP-2 mRNA levels were significantly decreased in scleral fibroblasts and RPE cells transfected with the miR-29a mimics. The secretion of MMP-2 by scleral fibroblasts and RPE cells was significantly decreased in cells transfected with the miR-29a mimics. CONCLUSIONS: Suppression of scleral fibroblast and RPE cell expression and secretion of MMP-2 by miR-29a can be used as a therapeutic target for the prevention and treatment of myopia.

miRNA profiling in the mice in response to Echinococcus multilocularis infection.

miRNAs are small non-coding regulatory RNAs and actively contribute to the pathogenesis of parasitic diseases in multiple ways. The influence of Echinococcus multilocularis infection on host miRNAs remains unclear. Herein, it was shown that E. multilocularis infection disturbed the expression of 4 of 10 genes essential to miRNA biogenesis in the mouse liver, including ago1, ago4, tarbp2 and xrn2. Comparative analysis of deep sequencing data identified 46 differentially expressed miRNAs with 93.5% (43/46) being down-regulated, some of which are associated with modulation of liver cell death and fibrosis, and GO analysis revealed that these miRNAs were mainly enriched in signal transduction (p<0.008). Moreover, 57 miRNAs were commonly found to be edited in complex patterns in both control and E. multilocularis-infected samples. In some miRNAs, editing of nucleotides at the same or/and distinct positions in a given miRNA occurred in different frequencies. Correlation analysis showed that the mutation and editing rates of 57 commonly edited miRNAs were significantly correlated between both samples (r=0.9974, p<0.0001), suggesting little effect of E. multilocularis infection on miRNA mutation and editing. These results provide a rich and informative data for further studies of a role of host miRNAs during E. multilocularis infection.

Dose Dependent Dual Effect of Baicalin and Herb Huang Qin Extract on Angiogenesis.

Huang Qin (root of Scutellaria baicalensis) is a widely used herb in different countries for adjuvant therapy of inflammation, diabetes, hypertension, different kinds of cancer and virus related diseases. Baicalin is the main flavonoid in this herb and has been extensively studied for 30 years. The angiogenic effect of herb Huang Qin extract and baicalin was found 13 years ago, however, the results were controversial with pro-angiogenic effect in some studies and anti-angiogenic effect in others. In this paper, the angiogenic effect of baicalin, its aglycone form baicalein and aqueous extract of Huang Qin was studied in chick embryo chorioallantoic membrane (CAM) model. Dose dependent dual effect was found in both aqueous extract and baicalin, but not in baicalein, in which only inhibitory effect was observed. In order to reveal the cellular and molecular mechanism of how baicalin and baicalein affect angiogenesis, cell proliferation and programmed cell death assays were performed in treated CAM. In addition, quantitative PCR array including 84 angiogenesis related genes was used to detect high and low dosage of baicalin and baicalein responsive genes. Low dose baicalin increased cell proliferation in developing blood vessels through upregulation of multiple angiogenic genes expression, but high dose baicalin induced cell death, performing inhibitory effect on angiogenesis. Both high and low dose of baicalein down regulated the expression of multiple angiogenic genes, decreased cell proliferation, and leads to inhibitory effects on angiogenesis.

Optimization of N-aryl-6-methoxy-1,2,3,4-tetrahydroquinolines as tubulin polymerization inhibitors.

Thirteen new N-aryl 1,2,3,4-tetrahydroquinoline compounds (4a-f, 6a-c, and 8a-d) were synthesized and evaluated for antitumor activity and drug-like properties. Compound 4a exhibited high inhibitory potency with low nanomolar GI50 values of 16-20 nM in cellular assays, including excellent activity against the P-glycoprotein overexpressing cell line KBvin. Compound 4a inhibited colchicine binding to tubulin and tubulin assembly with an IC50 value of 0.85 µM, superior to the reference compound CA4 (1.2 µM) in the same assay. In addition, 4a also exhibited highly improved water solubility (75 µg/mL) and a suitable logP value (3.43) at pH 7.4. With a good balance between antitumor potency and drug-like properties, compound 4a could be a new potential drug candidate for further development. Current results on SAR studies and molecular modeling provided more insight about this class of compounds as tubulin polymerization inhibitors targeting the colchicine site.

MMP-2, MMP-3, TIMP-1, TIMP-2, and TIMP-3 protein levels in human aqueous humor: relationship with axial length.

PURPOSE: We measured the aqueous humor levels of matrix metalloproteinases (MMP) MMP-1, MMP-2, MMP-3, and tissue inhibitors of matrix metalloproteinases (TIMP) TIMP-1, TIMP-2, and TIMP-3 in patients with myopia or cataract, and investigated the relationship between their levels and axial length (AL). METHODS: We measured MMP/TIMPs levels with the Luminex xMAP Technology by using commercially available Milliplex xMAP Kits. A total of 65 aqueous humor samples was collected from patients with myopia or cataract during cataract or clear lens extraction surgery. According to the AL, the samples were divided into three groups: group A, AL ≤ 24 mm; group B, AL 24 to 26 mm; and group C, AL ≥ 26 mm. RESULTS: Levels of MMP-2, MMP-3, TIMP-1, TIMP-2, and TIMP-3 could be detected in the aqueous humor. The levels of MMP-2, TIMP-1, TIMP-2, and TIMP-3 were positively correlated with AL. The differences of the levels of these MMPs/TIMPs among the three groups were statistically significant. The MMP-3 levels were not correlated with AL and there was no significant difference in MMP-3 levels among these three groups. Levels of MMP-1 could not be detected in the aqueous humor samples. CONCLUSIONS: Elevated levels of aqueous MMP-2, TIMP-1, TIMP-2, and TIMP-3 were found in the eyes with elongated axis.