Significant Changes of Corneal Astigmatism After Levator Muscle Surgery for Acquired Blepharoptosis.

PURPOSE: To investigate the change of corneal astigmatism after the correction of blepharoptosis. METHODS: This was a single-center retrospective cohort study conducted in Taiwan from 2017 to 2021. The medical records of patients with acquired blepharoptosis who had received levator muscle surgeries were collected. The differences in corneal astigmatism between the measurements before and at least 1 month after surgeries were investigated. Subgroup analysis of various severities of blepharoptosis and different types of corneal astigmatism was performed to determine their impacts on the axial changes after blepharoptosis surgeries. RESULTS: A total of 120 eyes of 68 patients were enrolled in this study. The mean axial change of corneal astigmatism was 17.4° after blepharoptosis surgeries, and 55 eyes (45.8%) had a change of at least 10°. In the subgroup analysis, the eyes with against-the-rule, with-the-rule, and oblique astigmatism had 42.9%, 68.4%, and 91.7% with an axial change of at least 10° after surgeries, respectively. The averaged axial change of corneal astigmatism after surgeries was 22.7° in eyes with severe blepharoptosis (margin to reflex distance1 < 1 mm), whereas it was 12.0° in eyes with mild-to-moderate blepharoptosis (margin to reflex distance1 ≥ 1 mm). CONCLUSIONS: A high proportion of eyes had a crucial axial change in corneal astigmatism after blepharoptosis surgeries, especially in those with oblique astigmatism and severe blepharoptosis. For blepharoptosis patients needing refractive surgeries or astigmatism correction with toric intraocular lens implantation, a surgical correction of blepharoptosis may be considered beforehand.

Real-world experience on intravitreal dexamethasone implant in patients with macular edema scheduled to undergo cataract surgery.

BACKGROUND: Patients with pre-existing macular edema (ME) due to diabetes and retinal vein occlusions (RVO) make up a growing population receiving cataract surgery. Surgery is associated with an increased risk of worsening existing ME due to post-surgical inflammation that can be further exacerbated by pre-existing diabetic retinopathy (DR) and retinal vein occlusion. This study aimed to examine the pre-operative use of intravitreal dexamethasone (DEX) implants in patients with ME undergoing cataract surgery. METHODS: A retrospective study was conducted at National Cheng Kung University Hospital in Taiwan involving 19 eyes of 16 patients with DME or ME associated with RVO. All participants received a DEX implant at baseline and underwent phacoemulsification within 3 months after its insertion. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) and central subfield thickness (CST) were evaluated. RESULTS: DEX implants reduced the CST from baseline (357.8 µm) to pre-surgery (280.8 µm). This reduction below baseline continued to month 6 post-surgery (319.4 µm). From baseline (16.15 mmHg), the mean IOP initially increased pre-surgery (17.78 mmHg) before returning to the baseline value at month 6 post-surgery (16.15 mmHg). All patients improved their BCVA from logMAR 0.943 on average at baseline to logMAR 0.532 at month 6 post-surgery. CONCLUSIONS: The results of the study suggested that patients with ME could benefit from DEX implants before cataract surgery within 3 months to achieve sufficient postoperative inflammation management and limit ME deterioration. DEX implants did not increase IOP post-surgery and was similar to baseline levels.

Outcomes of lacrimal punctal tumors treated with a superpulse CO2 laser.

Literature on lacrimal punctal tumors is limited due to their rarity. Our aim in this study was to evaluate the clinicopathological characteristics of these tumors and assess functional and aesthetic outcomes after CO2 laser ablation with silicone stent intubation. A retrospective consecutive study was conducted from December 2013 to November 2020. All patients who received CO2 laser ablation with silicone intubation for their punctal tumors at National Cheng Kung University Hospital, a tertiary hospital in Taiwan, were included in this study. Demographic and clinical information was gathered during preoperative and follow-up visits. Thirty-three Han Chinese patients with a solitary punctal tumor were included in this study. Demographically, we found a female predominance (75.8%), and most tumors were located at the lower punctum (69.7%). The incidence of melanocytic nevus was higher in punctal tumors (78.8%) than in benign eyelid tumors (22.3%). Irrigation tests were performed in the 33 patients during follow-up visits, all of whom exhibited patency of the lacrimal system. No patient complained of epiphora after surgery. Thirty-two patients (97%) were satisfied with the aesthetic outcome after surgery. Superpulse CO2 laser ablation followed by silicone stent intubation is a safe and effective treatment for benign punctal tumors. In addition, compared to those of eyelid tumors, the clinicopathological characteristics of lacrimal punctal tumors are different, and melanocytic nevus was the main cause of these tumors.

Structure of native oligomeric Sprouty2 by electron microscopy and its property of electroconductivity.

Receptor tyrosine kinases (RTKs) regulate many cellular processes, and Sprouty2 (Spry2) is known as an important regulator of RTK signaling pathways. Therefore, it is worth investigating the properties of Spry2 in more detail. In this study, we found that Spry2 is able to self-assemble into oligomers with a high-affinity KD value of approximately 16nM, as determined through BIAcore surface plasmon resonance analysis. The three-dimensional (3D) structure of Spry2 was resolved using an electron microscopy (EM) single-particle reconstruction approach, which revealed that Spry2 is donut-shaped with two lip-cover domains. Furthermore, the method of energy dispersive spectrum obtained through EM was analyzed to determine the elements carried by Spry2, and the results demonstrated that Spry2 is a silicon- and iron-containing protein. The silicon may contribute to the electroconductivity of Spry2, and this property exhibits a concentration-dependent feature. This study provides the first report of a silicon- and iron-containing protein, and its 3D structure may allow us (1) to study the potential mechanism through the signal transduction is controlled by switching the electronic transfer on or off and (2) to develop a new type of conductor or even semiconductor using biological or half-biological hybrid materials in the future.

"Etiology of trichiasis/distichiasis and its management with CO2 laser ablation".

BACKGROUND: Many techniques have been used to treat trichiasis/distichiasis, but none of them are consistently successful, without complications, or effective in different severities. Additionally, etiologic factors and their relationship with the severity or prognosis has not been identified in non-trachoma-endemic area. METHODS: In this retrospective consecutive study, we enrolled patients with trichiasis or distichiasis who had undergone CO2 laser ablation in our tertiary medical center between November 2013 and May 2022. Surgical success was defined as no regrowth of misdirected eyelashes for at least 3 months postoperatively. We recorded the success rate within three months and one year after one treatment session, and within three treatment sessions. We also investigated the relationship between etiologic factors, severity, and the success rate. RESULTS: We enrolled 216 eyelids of 137 patients (average age: 69.4 years, mean follow-up durations: 22.9 months). The major underlying causes of trichiasis/distichiasis were idiopathic (64.4%) and prior eyelid surgery (20.8%). More major trichiasis/distichiasis was observed among patients aged <60 years than that in patients aged ≥60 years (43% vs. 21%, p<0.01), and among patients with an underlying cause of prior eyelid surgery compared to patients with idiopathic etiology (42.2% vs. 23.0%, p<0.01). The success rates within three months and within one year after one treatment session, and within three treatment sessions were 87.5%, 76.2%, and 94.4%. CONCLUSIONS: Our study demonstrated idiopathic etiology and prior eyelid surgery are common causes of trichiasis/distichiasis. CO2 laser ablation is a safe, effective, and efficient treatment modality.

Balloon Dacryocystoplasty with Pushed Monocanalicular Intubation as a Primary Management for Primary Acquired Nasolacrimal Duct Obstruction.

Given the improvement in the instrument and techniques, novel surgical interventions emerged to avoid the osteotomy from the gold standard dacryocystorhinostomy (DCR) for treating primary acquired nasolacrimal duct obstruction (PANDO). This study's aim is to compare the surgical outcomes of antegrade balloon dacryocystoplasty (DCP) with pushed monocanalicular intubation (MCI) to balloon DCP alone in patients with complete PANDO. Adult patients with complete PANDO receiving balloon DCP followed by pushed MCI or balloon DCP alone from December 2014 to May 2019 were retrospectively reviewed. A total of 37 eyes of 29 patients were treated with balloon DCP with pushed MCI for 1 month, whereas 35 eyes of 28 patients were treated with balloon DCP alone. The success rates at 1 month, 3 months, and 6 months after operation were 89.2%, 73.0%, and 70.2%, respectively, in balloon DCP with MCI group, and 62.9%, 62.9%, and 60.0%, respectively, in the balloon DCP alone group. The balloon DCP with pushed MCI group had a better success rate but only reached statistical significance at 1 month postoperatively (p < 0.01). Subgroup analysis was performed based on age. The success rate in those under 65 in the combined balloon DCP with MCI group was significantly higher than in balloon DCP alone group (72.7% vs. 9.1%, p = 0.004), whereas there was no significant difference between those aged at least 65 in the combined group and the balloon DCP alone group (69.2% vs. 83.3%, p = 0.2). Conclusively, there was no significant difference in the success rate between antegrade balloon DCP with and without pushed MCI in general. Nevertheless, the former procedure was associated with significantly higher surgical success rate than the latter in younger patients.

Case Report: Botulinum Toxin-A for Complication of Exposure Keratopathy Following Frontalis-Orbicularis Oculi Muscle Flap Shortening.

Background: Lagophthalmos with exposure keratopathy is a potential vision-threatening complication following surgery for blepharoptosis. We report three cases successfully treated with botulinum toxin-A (Botox®, Allergan, Irvine, USA) for this complication. Cases: Three patients presented with severe blepharoptosis after surgery for orbital and frontal base tumors. They obtained good appearances after frontalis-orbicularis oculi muscle (FOOM) flap shortening. However, exposure keratopathy developed after the surgery despite frequent use of topical lubricants and autologous serum eye drops. We injected 5-10 units of botulinum toxin-A around the central supra-brow area, which was near the origin of the FOOM flap. One week later, they developed ptosis and could close the eye completely. The corneal defect gradually resolved. They recovered from ptosis 3 months later and never required a second injection. Observations: Lagophthalmos with exposure keratopathy is a potential vision-threatening complication following FOOM flap surgery. In severe cases, surgical revision should be considered to partially or totally release the FOOM flap attachment, which also decreases its function permanently. In this case series, we demonstrated that injecting botulinum toxin-A may be a promising method to manage this complication without permanently affecting the function of the FOOM flap. Conclusions: A botulinum toxin-A injection may be an effective treatment for patients developing exposure keratopathy after FOOM flap surgery.

Endoscopic dacryocystorhinostomy with short-term, pushed-type bicanalicular intubation vs. pulled-type monocanalicular intubation for primary acquired nasolacrimal duct obstruction.

Dacryocystorhinostomy (DCR) has been a primary treatment for adults with nasolacrimal duct obstruction, while the optimal approach and technique remain controversial. With the advancement of endoscopic DCR and the silicone stents, an update of the surgical outcomes and preferable approaches is required. This study aims at comparing the surgical outcomes of endoscopic DCR using pushed bicanalicular intubation (BCI) to pulled monocanalicular intubation (MCI) in adults with primary acquired nasolacrimal duct obstruction (PANDO). Forty five eyes of 45 patients were enrolled, including 22 eyes of 22 patients treated with endoscopic DCR with pulled MCI and 23 eyes of 23 patients with pushed BCI from January 2014 to June 2021. The success rates at stent removal, 1 month and 3 months after removal were 95, 91, and 82%, respectively, in the MCI group, and 100, 87, and 87% in the BCI group. The BCI group had better success rates but failed to reach a significant difference (p = 0.49, p = 0.67, p = 0.24, respectively). After analyzing with binary logistic regression, the implant material was demonstrated as the predictive of surgical success (p = 0.045). There was no significant difference in success rates between patients with dacryocystitis and those without dacryocystitis. We conclude that endoscopic DCR with pushed BCI is easily manipulated and has a promising surgical outcome over pulled MCI. Stent indwelling duration as well as history of dacryocystitis have less influence on the success rates.

Hyperviscosity-related retinopathy and serous macular detachment in Waldenström's macroglobulinemia: A mortal case in 5 years.

PURPOSE: To present a 5-year mortal case of Waldenström's macroglobulinemia-related retinopathy and serous macular detachment. CASE REPORT: A 63-year-old man, with unremarkable medical history, presented with bilateral decreased vision for 2 months. Fundus examination revealed bilateral scattered retinal hemorrhages, exudates, venous tortuosity, and serous macular detachment. Hematologic and biochemistry profiles showed pancytopenia with blood smear demonstrating erythrocyte rouleaux formation. Hyperviscosity syndrome was suspected and later Waldenström's macroglobulinemia was diagnosed by bone marrow biopsy and high concentration of serum IgM. Plasmapheresis and subsequent chemotherapy were arranged. In spite of resolution of most retinal abnormalities, his visual acuity still showed no improvement with a persistent bilateral macular detachment. The patient then died 5 years after the diagnosis of Waldenström's macroglobulinemia. CONCLUSIONS: Long-term toxicity of IgM to the retinal pigment epithelium may impede the resolution of the persistent serous macular detachment, resulting in an inability of recovery in his vision. Therefore, early diagnosis and timely reduction of serum paraproteins by plasmapheresis and chemotherapy is critical for preventing permanent damages to patients' health and vision.

Long-Term Outcome of Treatment with 2% Topical Ganciclovir Solution in Cytomegalovirus Anterior Uveitis and Corneal Endotheliitis.

Purpose: This study aimed to evaluate the therapeutic efficacy and long-term outcomes of treatment with topical 2% ganciclovir solution in immunocompetent patients with aqueous humor polymerase chain reaction (PCR)-proven cytomegalovirus (CMV) anterior uveitis and corneal endotheliitis. Methods: We retrospectively reviewed the findings for immunocompetent patients diagnosed with CMV uveitis or endotheliitis based on clinical manifestations and polymerase chain reaction (PCR) examination results and treated with topical 2% ganciclovir solution at National Cheng Kung University Hospital. Clinical outcome measurements included evaluations of the response rate, relapses, resolution of anterior chamber inflammation, visual acuity, and intraocular pressure. Results: The study included 38 eyes of 32 patients. Long-term administration of topical 2% ganciclovir significantly decreased keratic precipitates (p = 0.001), anterior chamber cells (p = 0.001), and reduced intraocular pressure (p < 0.001). Only one eye was unresponsive to topical ganciclovir treatment, and the recurrence decreased to 0.13 relapses per year. The presence of keratic precipitates and higher intraocular pressure at the initial presentation were significantly associated with recurrence (p = 0.036 and p = 0.001, respectively). Conclusions: Long-term use of topical 2% ganciclovir solution is effective, safe, and applicable when commercialized ganciclovir gel is not available.

Lipemia retinalis with different therapeutic responses: A report of two cases.

Lipemia retinalis is characterized by retinal blood vessels that are creamy white in color and is considered to be directly correlated to serum triglyceride levels. It is a rare retinal manifestation, with typical serum triglyceride levels above 2500 mg/dL required for its expression. We report two cases of lipemia retinalis with hypertriglyceridemia who presented with different retinal pictures during a 5-year follow-up. One showed a normalization of retinal vessels even though the serum triglyceride level was still far more than 2500 mg/dL (4660 mg/dL), but the other had persistent creamy white discoloration despite decreases in serum triglyceride level to below 2500 mg/dL (1031 mg/dL). This suggests that the absolute serum triglyceride level may not be the sole determinant of the typical retinal manifestation. In spite of this, early detection that leads to timely treatment will assist in prevention of severe ocular and systemic vascular complications.

Concurrent Pseudomonas Periorbital Necrotizing Fasciitis and Endophthalmitis: A Case Report and Literature Review.

(1) Background: Necrotizing fasciitis (NF) is an infection involving the superficial fascia and subcutaneous tissue. Endophthalmitis is an infection within the ocular ball. Herein we report a rare case of concurrent periorbital NF and endophthalmitis, caused by Pseudomonas aeruginosa (PA). We also conducted a literature review related to periorbital PA skin and soft-tissue infections. (2) Case presentation: A 62-year-old male had left upper eyelid swelling and redness; orbital cellulitis was diagnosed. During eyelid debridement, NF with the involvement of the upper Müller's muscle and levator muscle was noted. The infection soon progressed to scleral ulcers and endophthalmitis. The eye developed phthisis bulbi, despite treatment with intravitreal antibiotics. (3) Conclusions: Immunocompromised individuals are more likely than immunocompetent hosts to be infected by PA. Although periorbital NF is uncommon due to the rich blood supply in the area, the possibility of PA infection should be considered in concurrent periorbital soft-tissue infection and endophthalmitis.

Conjunctival Expression of Toll-Like Receptor 3 Plays a Pathogenic Role in the Formation of Ultraviolet Light-Induced Pterygium.

Purpose: Toll-like receptor 3 (TLR3), as a damage-associated molecular pattern sensor, can detect self-RNA released from necrotic cells induced by ultraviolet B (UVB) radiation exposure. Pterygium formation is believed to be a tumorigenesis-like process induced by UVB exposure. In this study, we aimed to investigate the expression pattern of TLR3 in pterygium specimens and cultured pterygial epithelial cells (PECs). Methods: Human pterygium and ipsilateral pterygium-free conjunctiva from the same patients were used in this study. The expression of TLR3 and nuclear factor-kappa B (NF-κB) was investigated in these specimens. PECs were exposed to UVB radiation to determine the effect of UVB on the expression of TLR3 and the activation of NF-κB. Results: The immunofluorescence study showed stronger TLR3 expression in superficial epithelial cells in the pterygial epithelium in comparison with the normal conjunctival epithelium. The expression of TLR3 decreased in intensity from the superficial epithelium toward the basal cell layer, implying a correlation between UVB exposure and TLR3 expression. Differential TLR3 expression patterns in pterygial and conjunctival tissues were also found in quantitative PCR analyses. PECs after UVB irradiation had higher protein levels of TLR3 and phospho-NF-κB than those of the PECs without irradiation. Immunofluorescence studies showed that UVB irradiation induced the nuclear translocation of NF-κB in the PECs. In PECs with the targeted TLR3 gene silencing, the expression of phospho-NF-κB was not induced by UVB irradiation. Conclusions: Our results indicate that UVB exposure, TLR3 expression, and NF-κB activation may be a critical sequence that leads to the formation of pterygium.

Surgical Outcomes of Balloon Dacryocystoplasty Combined With Pushed-Type Monocanalicular Intubation as the Primary Management for Congenital Nasolacrimal Duct Obstruction.

PURPOSE: To report the surgical outcomes of antegrade balloon dacryocystoplasty combined with pushed-type monocanalicular intubation as a primary surgical treatment in patients with congenital nasolacrimal duct obstruction. METHODS: A retrospective cohort study was conducted at National Cheng Kung University Hospital. The medical records of all patients with congenital nasolacrimal duct obstruction who underwent antegrade balloon dacryocystoplasty followed by pushed-type monocanalicular intubation as the primary surgical treatment from January 2018 to July 2020 were included. The monocanalicular tube was removed 1 to 2 weeks after intubation. Surgical success was defined as resolved epiphora 1 month after the tube was removed. RESULTS: A total of 62 eyes of 48 patients were involved in this study. The mean age of the total population was 24.1 months (range: 12 to 66 months). The mean duration of the tube indwelling in the nasolacrimal duct was 9.5 days (range: 4 to 15 days). A total of 60 of the 62 eyes (96.77%) reported surgical success. Early tube loss occurred in 2 eyes (3.23%); however, epiphora was not reported afterward. No complications other than tube loss were recorded. There were no recurrences in patients who had undergone successful surgery observed up to July 2020. CONCLUSIONS: Antegrade balloon dacryocystoplasty with short-term pushed-type monocanalicular intubation as a primary surgical treatment for congenital nasolacrimal duct obstruction may have high potential with a high success rate and a low complication rate. [J Pediatr Ophthalmol Strabismus. 2021;58(6):365-369.].

Structure, mechanistic action, and essential residues of a GH-64 enzyme, laminaripentaose-producing beta-1,3-glucanase.

Laminaripentaose-producing beta-1,3-glucanase (LPHase), a member of glycoside hydrolase family 64, cleaves a long-chain polysaccharide beta-1,3-glucan into specific pentasaccharide oligomers. The crystal structure of LPHase from Streptomyces matensis DIC-108 was solved to 1.62 A resolution using multiple-wavelength anomalous dispersion methods. The LPHase structure reveals a novel crescent-like fold; it consists of a barrel domain and a mixed (alpha/beta) domain, forming a wide-open groove between the two domains. The liganded crystal structure was also solved to 1.80 A, showing limited conformational changes. Within the wide groove, a laminaritetraose molecule is found to sit in an electronegatively charged central region and is proximal to several conserved residues including two carboxylates (Glu(154) and Asp(170)) and four other sugar-binding residues (Thr(156), Asn(158), Trp(163), and Thr(167)). Molecular modeling using a laminarihexaose as a substrate suggests roles for Glu(154) and Asp(170) as acid and base catalysts, respectively, whereas the side chains of Thr(156), Asn(158), and Trp(163) demarcate subsite +5. Site-directed mutagenesis of Glu(154) and Asp(170) confirms that both carboxylates are essential for catalysis. Together, our results suggest that LPHase uses a direct displacement mechanism involving Glu(154) and Asp(170) to cleave a beta-1,3-glucan into specific alpha-pentasaccharide oligomers.

Modified Hotz procedure with CO2 laser ablation of the orbicularis oculi muscle for epiblepharon.

OBJECTIVE: To introduce the use of a CO2 laser for ablation of the orbicularis oculi muscle (OOM) in a modified Hotz procedure for correction of epiblepharon and to report its clinical outcome. METHODS: A retrospective consecutive study was conducted from August 2014 to January 2018. Patients who had undergone surgical correction for epiblepharon with the modified Hotz procedure and a CO2 laser ablation of OOM were included. The procedure includes a transverse subciliary incision with removal of a very small amount of skin using CO2 laser ablation. The ablation was carried out continuously on parts of the pretarsal portion and parts of the preseptal portion of the OOM inferior to the lower edge of the incised skin. Finally, the incised skin was closed and secured to the tarsus. The patients were followed for direct inspection of the wound, the direction of the lashes, and the status of the cornea. RESULTS: One hundred eyelids from 50 patients were enrolled. The average age was 6.4 years. The mean postoperative follow-up period was 14.3 months. In 90 eyelids (90.0%), the eyelashes were successfully outwardly everted. Undercorrections were noted in 10 eyelids (10.0%). To date, the cosmetic outcome was satisfactory in all cases without complications such as wound dehiscence, ectropion, and eyelid retraction. CONCLUSIONS: A CO2 laser is a safe and effective alternative to the scalpel in the modified Hotz procedure to correct epiblepharon. Its advantages include limited skin excision, minimal bleeding during surgery, short operation time, and a satisfactory clinical outcome.

Postoperative Mycobacteroides abscessus subsp. abscessus endophthalmitis: Clinical analysis of 12 clustered adults and a proposed therapeutic algorithm.

PURPOSE: Postoperative endophthalmitis caused by nontuberculous mycobacterium is a rare but devastating complication after intraocular surgery. However, optimal treatment strategies remain undetermined in view of its rarity. METHODS: We investigated the cases of culture-proven postoperative Mycobacteroides abscessus subsp. abscessus endophthalmitis in southern Taiwan, focusing on clinical manifestations and microbiological study, and aimed to describe clinical staging and to propose a therapeutic modality for this disease. RESULTS: Twelve cases, including two published cases, were treated in two medical centers in southern Taiwan between Aug. 2011 and Dec. 2016, and all ever received cataract surgery at one clinic. Their disease courses could be categorized into four distinct stages, i.e., the initial, quiescent, recurrent, and end stage, and some cases experienced 1-4 cycles of quiescent-recurrent stages. Although all eyes ended up with phthisis or were eviscerated, the affected eyes receiving pars plana vitrectomy (PPV) tended to become quiescent and survived longer than those without PPV (adjusted hazard ratio: 13.9, p < 0.05). Eight isolates of eight patients were available for microbiological study. All isolates were susceptible to amikacin, and inducible clarithromycin resistance was observed in 100% of isolates. CONCLUSION: Despite the preservation of vision in postoperative M.abscessus endophthalmitis remained a challenge, a stage-based approach is proposed, which may facilitate decision-makings for the future study.

Production of multivalent protein binders using a self-trimerizing collagen-like peptide scaffold.

A class of multivalent protein binders was designed to overcome the limitations of low-affinity therapeutic antibodies. These binders, termed "collabodies," use a triplex-forming collagen-like peptide to drive the trimerization of a heterologous target-binding domain. Different forms of collabody, consisting of the human single-chain variable fragment (scFv) fused to either the N or C terminus of the collagen-like peptide scaffold (Gly-Pro-Pro)(10), were stably expressed as soluble secretory proteins in mammalian cells. The collabody consisting of scFv fused to the N terminus of collagen scaffold is present as a homotrimer, whereas it exhibited a mixture of trimer and interchain disulfide-bonded hexamer when cysteine residues were introduced and flanked the scaffold. The collagenous motif in collabody is prolyl-hydroxylated, with remarkable thermal and serum stabilities. The collabody erb_scFv-Col bound to the extracellular domain of epidermal growth factor receptor with a binding strength approximately 20- and 1000-fold stronger than the bivalent and monovalent counterparts, respectively. The trimeric collagen scaffold does not compromise the functionality of the binding moieties of parental immunoglobulin G (IgG); therefore, it could be applied to fuse other protein molecules to acquire significantly improved targeting-binding strengths.