Comprehensive insights into a decade-long journey: The evolution, impact, and human factors of an asynchronous telemedicine program for diabetic retinopathy screening in Pennsylvania, United States.

Diabetic Retinopathy stands as a leading cause of irreversible blindness, necessitating frequent examinations, especially in the early stages where effective treatments are available. However, current examination rates vary widely, ranging from 25-60%. This study scrutinizes the Point-of-Care Diabetic Retinopathy Examination Program at the University of Pittsburgh/UPMC, delving into its composition, evolution, challenges, solutions, and improvement opportunities. Employing a narrative approach, insights are gathered from key stakeholders, including ophthalmologists and staff from primary care clinics. A quantitative analysis from 2008 to 2020 provides a comprehensive overview of program outcomes, covering 94 primary care offices with 51 retinal cameras. Program components feature automated non-mydriatic 45° retinal cameras, a dedicated coordinator, rigorous training, and standardized workflows. Over this period, the program conducted 21,960 exams in 16,458 unique individuals, revealing a diverse population with an average age of 58.5 and a balanced gender distribution. Average body mass index (33.96±8.02 kg/m2) and hemoglobin A1c (7.58%±1.88%) surpassed normal ranges, indicating prevalent risk factors for diabetes-related complications. Notably, 24.2% of patients underwent more than one exam, emphasizing program engagement. Findings indicated that 86.3% of exams were gradable, with 59.0% within normal limits, 12.1% showing some evidence of diabetic retinopathy, and 6.4% exhibiting vision-threatening diabetic retinopathy. Follow-up appointments with ophthalmologists were recommended in 31.5% of exams due to indeterminate results, positive diabetic retinopathy (≥moderate or macular exudate), or other findings like age-related macular degeneration or suspected glaucoma. The program demonstrated high reproducibility across diverse healthcare settings, featuring a sustainable model with minimal camera downtime, standardized workflows, and financial support from grants, health systems, and clinical revenues. Despite COVID-19 pandemic challenges, this research emphasizes the program's reproducibility, user-friendly evolution, and promising outcomes. Beyond technical contributions, it highlights human factors influencing program success. Future research could explore adherence to follow-up ophthalmological recommendations and its associated factors.

Challenges in posterior uveitis-tips and tricks for the retina specialist.

PURPOSE: Posterior uveitis is a common chorioretinal pathology affecting all ages worldwide and is a frequent reason for referral to the retina clinic. The spectrum of etiologies for uveitis is very broad and includes infectious and auto-immune diseases. Inflammation can be confined to the eye or may be a part of systemic disease. A useful outline is therefore proposed to aid in the correct diagnosis of these challenging entities. The situation is further complicated by the fact that many neoplastic conditions resemble features of posterior uveitis; they are known as "masqueraders of uveitis". Here, we summarize different posterior uveitides that present with rare findings, along with masqueraders that can be difficult to distinguish. These conditions pose a diagnostic dilemma resulting in delay in treatment because of diagnostic uncertainty. METHODS: An extensive literature search was performed on the MEDLINE/PUBMED, EBSCO and Cochrane CENTRAL databases from January 1985 to January 2022 for original studies and reviews of predetermined diagnoses that include posterior uveitic entities, panuveitis and masquerade syndromes. RESULTS: We described conditions that can present as mimickers of posterior uveitis (i.e., immune check-points inhibitors and Vogt-Koyanagi-Harada-like uveitis; leukemia and lymphoma associated posterior uveitis), inflammatory conditions that present as mimickers of retinal diseases (i.e., Purtscher-like retinopathy as a presentation of systemic lupus erythematosus; central serous chorioretinopathy masquerading inflammatory exudative retinal detachment), and uveitic conditions with rare and diagnostically challenging etiologies (i.e., paradoxical inflammatory effects of anti-TNF-α; post vaccination uveitis; ocular inflammation after intravitreal injection of antiangiogenic drugs). CONCLUSION: This review of unique posterior uveitis cases highlights the overlapping features of posterior uveitis (paradoxical inflammatory effects of anti -TNF α and uveitis; Purtscher-like retinopathy as a presentation of systemic lupus erythematosus, …) and the nature of retinal conditions (ischemic ocular syndrome, or central retinal vein occlusion, amyloidosis, inherited conditions like retinitis pigmentosa, autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), etc.…) that may mimic them is represented. Careful review of past uveitis history, current medications and recent vaccinations, detailed examination of signs of past or present inflammation, eventually genetic testing and/ or multimodal retinal imaging (like fluorescein angiography, EDI-OCT, OCT-angiography for lupus Purtscher-like retinopathy evaluation, or ICG for central serous retinopathy, or retinal amyloid angiopathy) may aid in correct diagnosis.

Coagulase-negative staphylococcal endophthalmitis: clinical severity and outcomes based on speciation.

OBJECTIVE: To identify characteristics and visual outcomes of coagulase-negative staphylococcal (CoNS) endophthalmitis in the era after the Endophthalmitis Vitrectomy Study. DESIGN: Single-centre retrospective analysis. PARTICIPANTS: Forty-two samples from 40 patients with documented CoNS endophthalmitis. METHODS: Visual acuity outcomes of CoNS endophthalmitis were assessed in relation to species and type of treatment instituted (i.e., pars plana vitrectomy [PPV] versus vitreous tap and injection of intravitreal antibiotics [T&I]) on 42 samples from 40 patients. RESULTS: Staphylococcus epidermidis was the most prevalent CoNS in our study. Cataract surgery and intravitreal injections were the most common sources for acute CoNS endophthalmitis. Eyes presenting with hand motion or better vision had similar mean final vision after either intravitreal antibiotics or PPV, whereas those with light perception or worse vision at onset had better outcomes after PPV only. Subanalysis showed that patients with S. epidermidis endophthalmitis (n = 39 eyes) had similar visual outcomes with either intravitreal injections or PPV regardless of visual acuity. Hypopyon and vitritis are not always present. CONCLUSIONS: Patients with S. epidermidis endophthalmitis may benefit similarly from either early vitrectomy or intravitreal antibiotic injections regardless of visual acuity. This finding may be a supplement to the complements the management standards set forth by the Endophthalmitis Vitrectomy Study.

Hidden in the Eyes-Recurrence of Systemic Hemopathies Reportedly "In Remission": Six Cases and Review of Literature.

Background and Objectives: Secondary ocular localizations of hematological malignancies are blinding conditions with a poor prognosis, and often result in a delay in the diagnosis. Materials and Methods: We describe a series of rare cases of ocular involvement in six patients with hematological malignancies, reportedly in remission, who presented secondary ocular localizations, challenging to diagnose. Two patients had an acute lymphoblastic leukemia (ALL) and developed either a posterior scleritis or a pseudo-panuveitis with ciliary process infiltration. One patient had iris plasmacytoma and developed an anterior uveitis as a secondary presentation. Two patients had a current systemic diffuse large B-cell lymphoma (DLBCL) and were referred either for intermediate uveitis or for papilledema and vitritis with secondary retinitis. Finally, one patient with an acute myeloid leukemia (AML) presented a conjunctival localization of a myeloid sarcoma. We herein summarize the current knowledge of ophthalmologic manifestations of extramedullary hematopathies. Results: Inflammatory signs were associated with symptomatic infiltrative lesions well displayed in either the iris, the retina, the choroid, or the cavernous sinus, from the admission of the patients in the ophthalmological department. These findings suggest that patients with ALL, AML, systemic DLBCL, and myeloma can present with ophthalmic involvement, even after having been reported as in remission following an effective systemic treatment and/or allograft. Conclusions: Early detection of hidden recurrence in the eyes may permit effective treatment. Furthermore, oncologists and ophthalmologists should be aware of those rare ocular malignant locations when monitoring patient's progression after initial treatment, and close ophthalmologic examinations should be recommended when detecting patient's ocular symptoms after treatment.

Review of the Current Literature and Our Experience on the Value of OCT-angiography in White Dot Syndromes.

PURPOSE: To describe the application of OCT-A in various posterior uveitis disorders in our experience and to compare it with the available literature. METHODS: Eighteen eyes with the diagnoses of multifocal choroiditis (MFC), multifocal placoid pigment epitheliopathy (APMPPE), multiple evanescent white dot syndrome (MEWDS), tuberculous serpiginous-like choroiditis (SLC), serpiginous choroiditis (SC), and birdshot chorioretinopathy (BSCR) were studied. RESULTS: We found flow void of the choriocapillaris in patients with APMPPE, SC, MFC, BSCR, and in SLC. In contrast, perfusion of the choriocapillaris seemed normal in patients with MEWDS. CONCLUSIONS: We confirmed that OCT-A contributes new information on the physiopathology of white dot syndromes and inflammatory chorioretinopathies, notably on whether or not the choriocapillaris is involved. Comparing the OCT-A features allowed us to suggest that both APMPPE and SLC might be part of the same spectrum of inflammatory disease with primary involvement at the level of the choriocapillaris and secondary RPE damage.

Long-term retinal changes in progressive geographic atrophy.

BACKGROUND: Age-related macular degeneration (AMD) is one of the leading causes of blindness with loss of retinal layers over long term. We aim to evaluate these changes in eyes with progressive non-exudative AMD with geographic atrophy (GA). METHODS: This retrospective study included patients with GA with a minimum of 4 years follow up. Retinal layers on spectral domain optical coherence tomography (SD-OCT) were segmented based on their reflectivity patterns using validated semi-automated segmentation algorithm. The thickness of the segmented retinal layers was measured. Horizontal length of GA at baseline and last follow-up were also measured. Regression analysis was performed to correlate changes in RPE layer thickness with other retinal layers and the length of GA on OCT. RESULTS: A total of 351-line scans including 17 foveal scans showing presence of GA at final visit that is, a total of 2457 retinal layer bands were analyzed. Outer nuclear layer (ONL) (p = 0.02), outer segment layers (OSL) (p = 0.01), and retinal pigment epithelium (RPE) (p = 0.01) showed a statistically significant variation between baseline and final visit. Regression analysis showed the change in ONL (r = 0.72; p = 0.01) and OSL (r = 0.93, p < 0.01) correlated significantly with change in RPE thickness whereas rest of the layers failed to show significant correlation. CONCLUSION: Outer retinal layers (ONL and OSL) show more significant and widespread changes in retinal thickness and correlated most significantly with RPE thickness changes in eyes with GA due to AMD. Assessment of various retinal layer bands can be used as surrogate quantitative parameters to study eyes with GA.

The full range of ophthalmological clinical manifestations in systemic lupus erythematosus.

Purpose: To determine the full range of ophthalmological clinical manifestations in systemic lupus erythematosus (SLE) and to compare the systemic features associated with them. Methods: Files of 13 patients with ocular SLE (n = 20 eyes) diagnosed as per the American College of Rheumatology (ACR) 2012 revised criteria were retrospectively reviewed. Results: The following clinical manifestations were found: keratoconjunctivitis sicca (n = three patients), anterior uveitis associated with an inflammatory pseudo-tumor orbital mass (n = one patient, one eye), episcleritis and periorbital edema (n = one patient, two eyes), posterior scleritis (n = one patient, two eyes), bilateral papillary edema in the context of idiopathic intracranial hypertension (n = one patient, one eye), inflammatory optic neuritis (n = one patient, one eye), and lupus retinopathies with varying degrees of capillary occlusions mainly arteriolar (n = seven patients, 13 eyes) and larger arteries or veins (retinal arteries occlusions and retinal veins occlusions) (n = one patient, two eyes). Some patients presented with combined ophthalmological manifestations.Systemic SLE was discovered by its ophthalmic manifestation in three cases (23%) and was previously known in the other 10 cases (77%). On average, ocular symptoms were seen 8 years after the initial diagnosis of SLE. Other systemic SLE disorders included cutaneous disorders (77%), joint disorders (38%), central nervous system (CNS) disorders (23%), renal disorders (38%), and oral ulcers (23%).Treatment of the ophthalmic system manifestations of lupus included local steroid therapies along with systemic immunosuppression.The most common laboratory ACR criteria were: high levels of antinuclear antibodies (ANA) (100%), positive anti-Sm (64%), anti-dsDNA (27%), low complement levels (27%), and positive antiphospholipid (APL) antibodies (18%). Discussion: SLE activity in the ophthalmic system is characterized by its functional severity and the range of involvement can be categorized by anatomical involvement: presence of anterior uveitis, episcleritis, scleritis, periorbital edema, posterior uveitis with retinal vascular ischemia, or papillary edema. Not currently part of the diagnosis criteria of the SLE ACR given its rarity, the ocular localization of the pathology led to the diagnosis of SLE in three cases; thus, developing a greater understanding of ocular lupus may help in identifying and treating systemic manifestations of lupus earlier.

Age-related macular degeneration masqueraders: From the obvious to the obscure.

Age-related macular degeneration (AMD) is one of the leading causes of blindness worldwide with increasing prevalence owing to increased life expectancy. Intravitreal injections of antivascular endothelial growth factor agents are commonly used in exudative AMD and oral antioxidant medication for nonexudative AMD; however, many disorders mimic exudative and nonexudative AMD, and misdiagnosis can seriously affect the management of these patients. We summarize the demographics and clinical and imaging characteristics of each of the conditions that masquerade as AMD. As some of the conditions have features of AMD, a short update on the classical features of AMD is also included.

RELATIVE QUIESCENCE OF EXUDATIVE AGE-RELATED MACULAR DEGENERATION AFTER RESOLUTION OF POSTINJECTION ENDOPHTHALMITIS.

PURPOSE: To evaluate alterations in treatment burden and course of exudative age-related macular degeneration in patients who contracted endophthalmitis from intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. METHODS: Retrospective study at the University of Pittsburgh Medical Center examining frequency of anti-VEGF injections, activity of choroidal neovascularization, and visual acuity before and after endophthalmitis treatment. RESULTS: Twenty-one patients meeting inclusion criteria were identified, of whom 7 (33%) patients did not restart anti-VEGF treatment 12 months after endophthalmitis because of quiescence of exudative age-related macular degeneration without significant visual acuity loss (P > 0.05). Patients who resumed anti-VEGF treatment exhibited 32% and 38% decreases in injection frequency by 12 and 24 months after endophthalmitis, respectively (P < 0.05). On first optical coherence tomography follow-up, 10 patients exhibited quiescence of choroidal neovascularization activity, although there were no measurable changes in macular thickness (P > 0.05). No differences in post-endophthalmitis exudative age-related macular degeneration progression or treatment burden were observed when factoring adjuvant intravitreal steroid therapy, culture results, nor choroidal neovascularization subtypes. CONCLUSION: Endophthalmitis resolution is associated with a decrease in choroidal neovascularization activity and a reduction of anti-VEGF treatment burden in patients with exudative age-related macular degeneration.

Palliative Care and Phase 1 Trials: Intervention to Improve Quality of Life and Provide Education
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BACKGROUND: Patients in phase 1 clinical trials often have significant symptom burdens and quality-of-life concerns that increase as they progress along the cancer trajectory and experience drug toxicities from the clinical trial. 
. OBJECTIVES: The interdisciplinary intervention described is aimed at providing optimum palliative care to support patients with solid tumors participating in a phase 1 clinical trial.
. METHODS: The intervention includes a baseline evaluation using quantitative surveys, a comprehensive palliative care assessment by a research nurse based on patient baseline evaluation, and a goals-of-care discussion by the treating oncologist. The second component includes an interdisciplinary meeting where palliative care recommendations are made, followed by two patient education sessions.
. FINDINGS: The initial experience with the palliative care intervention suggests a need for support for this population, as well as potential benefits from integrating palliative care for patients enrolled in phase 1 clinical trials.

The oral VEGF receptor tyrosine kinase inhibitor pazopanib in combination with the MEK inhibitor trametinib in advanced cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma is an aggressive malignancy with limited therapeutic options. MEK inhibition and antiangiogenic therapies have individually shown modest activity in advanced cholangiocarcinoma, whereas dual inhibition of these pathways has not been previously evaluated. We evaluated the safety and efficacy of combination therapy with the oral VEGF receptor tyrosine kinase inhibitor pazopanib plus the MEK inhibitor trametinib in patients with advanced cholangiocarcinoma. METHODS: In this open-label, multicentre, single-arm trial, adults with advanced unresectable cholangiocarcinoma received pazopanib 800 mg daily and trametinib 2 mg daily until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) with secondary end points including overall survival (OS), response rate, and disease control rate (DCR). RESULTS: A total of 25 patients were enrolled and had received a median of 2 prior systemic therapies (range 1-7). Median PFS was 3.6 months (95% CI: 2.7-5.1) and the 4-month PFS was 40% (95% CI: 24.7-64.6%). There was a trend towards increased 4-month PFS as compared with the prespecified null hypothesised 4-month PFS of 25%, but this difference did not reach statistical significance (P=0.063). The median survival was 6.4 months (95% CI: 4.3-10.2). The objective response rate was 5% (95% CI: 0.13-24.9%) and the DCR was 75% (95% CI: 51%, 91%). Grade 3/4 adverse events attributable to study drugs were observed in 14 (56%) and included thrombocytopenia, abnormal liver enzymes, rash, and hypertension. CONCLUSIONS: Although the combination of pazopanib plus trametinib had acceptable toxicity with evidence of clinical activity, it did not achieve a statistically significant improvement in 4-month PFS over the prespecified null hypothesised 4-month PFS.

IMAGING WITH MULTIMODAL ADAPTIVE-OPTICS OPTICAL COHERENCE TOMOGRAPHY IN MULTIPLE EVANESCENT WHITE DOT SYNDROME: THE STRUCTURE AND FUNCTIONAL RELATIONSHIP.

PURPOSE: To elucidate the location of pathological changes in multiple evanescent white dot syndrome (MEWDS) with the use of multimodal adaptive optics (AO) imaging. METHODS: A 5-year observational case study of a 24-year-old female with recurrent MEWDS. Full examination included history, Snellen chart visual acuity, pupil assessment, intraocular pressures, slit lamp evaluation, dilated fundoscopic exam, imaging with Fourier-domain optical coherence tomography (FD-OCT), blue-light fundus autofluorescence (FAF), fundus photography, fluorescein angiography, and adaptive-optics optical coherence tomography. RESULTS: Three distinct acute episodes of MEWDS occurred during the period of follow-up. Fourier-domain optical coherence tomography and adaptive-optics imaging showed disturbance in the photoreceptor outer segments (PR OS) in the posterior pole with each flare. The degree of disturbance at the photoreceptor level corresponded to size and extent of the visual field changes. All findings were transient with delineation of the photoreceptor recovery from the outer edges of the lesion inward. Hyperautofluorescence was seen during acute flares. Increase in choroidal thickness did occur with each active flare but resolved. CONCLUSION: Although changes in the choroid and RPE can be observed in MEWDS, Fourier-domain optical coherence tomography, and multimodal adaptive optics imaging localized the visually significant changes seen in this disease at the level of the photoreceptors. These transient retinal changes specifically occur at the level of the inner segment ellipsoid and OS/RPE line. En face optical coherence tomography imaging provides a detailed, yet noninvasive method for following the convalescence of MEWDS and provides insight into the structural and functional relationship of this transient inflammatory retinal disease.

Novel antifungal drug discovery based on targeting pathways regulating the fungus-conserved Upc2 transcription factor.

Infections by Candida albicans and related fungal pathogens pose a serious health problem for immunocompromised patients. Azole drugs, the most common agents used to combat infections, target the sterol biosynthetic pathway. Adaptation to azole therapy develops as drug-stressed cells compensate by upregulating several genes in the pathway, a process mediated in part by the Upc2 transcription factor. We have implemented a cell-based high-throughput screen to identify small-molecule inhibitors of Upc2-dependent induction of sterol gene expression in response to azole drug treatment. The assay is designed to identify not only Upc2 DNA binding inhibitors but also compounds impeding the activation of gene expression by Upc2. An AlphaScreen assay was developed to determine whether the compounds identified interact directly with Upc2 and inhibit DNA binding. Three compounds identified by the cell-based assay inhibited Upc2 protein level and UPC2-LacZ gene expression in response to a block in sterol biosynthesis. The compounds were growth inhibitory and attenuated antifungal-induced sterol gene expression in vivo. They did so by reducing the level of Upc2 protein and Upc2 DNA binding in the presence of drug. The mechanism by which the compounds restrict Upc2 DNA binding is not through a direct interaction, as demonstrated by a lack of DNA binding inhibitory activity using the AlphaScreen assay. Rather, they likely inhibit a novel pathway activating Upc2 in response to a block in sterol biosynthesis. We suggest that the compounds identified represent potential precursors for the synthesis of novel antifungal drugs.

The yeast anaerobic response element AR1b regulates aerobic antifungal drug-dependent sterol gene expression.

Saccharomyces cerevisiae ergosterol biosynthesis, like cholesterol biosynthesis in mammals, is regulated at the transcriptional level by a sterol feedback mechanism. Yeast studies defined a 7-bp consensus sterol-response element (SRE) common to genes involved in sterol biosynthesis and two transcription factors, Upc2 and Ecm22, which direct transcription of sterol biosynthetic genes. The 7-bp consensus SRE is identical to the anaerobic response element, AR1c. Data indicate that Upc2 and Ecm22 function through binding to this SRE site. We now show that it is two novel anaerobic AR1b elements in the UPC2 promoter that direct global ERG gene expression in response to a block in de novo ergosterol biosynthesis, brought about by antifungal drug treatment. The AR1b elements are absolutely required for auto-induction of UPC2 gene expression and protein and require Upc2 and Ecm22 for function. We further demonstrate the direct binding of recombinant expressed S. cerevisiae ScUpc2 and pathogenic Candida albicans CaUpc2 and Candida glabrata CgUpc2 to AR1b and SRE/AR1c elements. Recombinant endogenous promoter studies show that the UPC2 anaerobic AR1b elements act in trans to regulate ergosterol gene expression. Our results indicate that Upc2 must occupy UPC2 AR1b elements in order for ERG gene expression induction to take place. Thus, the two UPC2-AR1b elements drive expression of all ERG genes necessary for maintaining normal antifungal susceptibility, as wild type cells lacking these elements have increased susceptibility to azole antifungal drugs. Therefore, targeting these specific sites for antifungal therapy represents a novel approach to treat systemic fungal infections.

Cystoid macular edema in retinitis pigmentosa patients without associated macular thickening.

PURPOSE: To describe the occurrence of cystoid macular edema (CME) in the setting of central foveal thickness (CFT) under 250 µm as measured by optical coherence tomography (OCT) in patients with retinitis pigmentosa (RP). METHODS: Stratus OCT was used to measure CFT in a total of 90 eyes from 46 patients with RP. Cross-sectional OCT images were also evaluated for CME, which was defined as cystoid changes in the macula seen on at least two linear scans. RESULTS: CME was identified in 13 of the 46 patients or in 22 of 90 eyes by OCT. In eyes with macular edema, CFT ranged from 224 to 718 µm (mean = 339 ± 137 µm). In eyes without macular edema, CFT ranged from 99 to 273 µm (mean = 184 ± 40 µm). Bilateral CME occurred in 9 of 13 patients (69%). CFT was considered "normal" in 7 of the 22 eyes (32%) with CME. Two patients had bilateral CME with normal CFTs, under 250 µm. CONCLUSION: We demonstrate the occurrence of CME in RP patients without associated thickening, which has not been described. This concept likely is applicable to other diseases with retinal thinning.

Inhibition of a secreted glutamic peptidase prevents growth of the fungus Talaromyces emersonii.

The thermophilic filamentous fungus Talaromyces emersonii secretes a variety of hydrolytic enzymes that are of interest for processing of biomass into fuel. Many carbohydrases have been isolated and characterized from this fungus, but no studies had been performed on peptidases. In this study, two acid-acting endopeptidases were isolated and characterized from the culture filtrate of T. emersonii. One of these enzymes was identified as a member of the recently classified glutamic peptidase family and was subsequently named T. emersonii glutamic peptidase 1 (TGP1). The second enzyme was identified as an aspartyl peptidase (PEP1). TGP1 was cloned and sequenced and shown to exhibit 64 and 47% protein identity to peptidases from Aspergillus niger and Scytalidium lignocolum, respectively. Substrate profiling of 16 peptides determined that TGP1 has broad specificity with a preference for large residues in the P1 site, particularly Met, Gln, Phe, Lys, Glu, and small amino acids at P1' such as Ala, Gly, Ser, or Thr. This enzyme efficiently cleaves an internally quenched fluorescent substrate containing the zymogen activation sequence (k(cat)/K(m)=2 x 10(5) m(-1) s(-1)). Maximum hydrolysis occurs at pH 3.4 and 50 degrees C. The reaction is strongly inhibited by a transition state peptide analog, TA1 (K(i)=1.5 nM), as well as a portion of the propeptide sequence, PT1 (K(i)=32 nM). Ex vivo studies show that hyphal extension of T. emersonii in complex media is unaffected by the aspartyl peptidase inhibitor pepstatin but is inhibited by TA1 and PT1. This study provides insight into the functional role of the glutamic peptidase TGP1 for growth of T. emersonii.