Rose bengal-assisted green light photodynamic antimicrobial therapy (RB-PDAT) is a new approach being evaluated for treating infectious keratitis. Preliminary clinical evidence suggests the broad-spectrum antimicrobial activity of RB-PDAT. The therapy potentially exerts its activity by generating reactive oxygen species that inhibit microbial growth. Large clinical trials are underway to further establish a role for RB-PDAT in clinical medicine, especially recalcitrant fungal keratitis that is less responsive to conventional photodynamic therapy with riboflavin. A potential limitation of the therapy includes poor penetration of rose bengal dye into the cornea. This limitation is being addressed by several approaches, including lipophilic prodrugs, nanoparticles, and physical approaches for enhanced delivery, including iontophoresis and ultrasound.
GopinathanU, SharmaS, GargP, et al.Review of epidemiological features, microbiological diagnosis and treatment outcome of microbial keratitis: Experience of over a decade. Indian J Ophthalmol, 2009; 57(4):273–279; doi: 10.4103/0301-4738.53051
3.
UngL, BispoPJM, ShanbhagSS, et al.The persistent dilemma of microbial keratitis: Global burden, diagnosis, and antimicrobial resistance. Surv Ophthalmol, 2019; 64(3):255–271; doi: 10.1016/j.survophthal.2018.12.003
JosephJ, KaroliyaR, ShebaE, et al.Trends in the microbiological spectrum of nonviral keratitis at a single tertiary care ophthalmic hospital in India: A review of 30 years. Cornea, 2023; 42(7):837–846; doi: 10.1097/ICO.0000000000003105
6.
BrownL, LeckAK, GichangiM, et al.The global incidence and diagnosis of fungal keratitis. Lancet Infect Dis, 2021; 21(3):e49–e57; doi: 10.1016/S1473-3099(20)30448-5
7.
CollierSA, GronostajMP, MacGurnAK, et al.; Centers for Disease Control and Prevention (CDC). Estimated burden of keratitis–United States, 2010. MMWR Morb Mortal Wkly Rep, 2014; 63(45):1027–1030.
8.
Bin IsmailMA, LimRHF, FangHM, et al.Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS)—report 4: Analysis and outcome of scleritis in an East Asian population. J Ophthalmic Inflamm Infect, 2017; 7(1):6; doi: 10.1186/s12348-017-0124-5
9.
AbdulhalimBH, WagihMM, GadAAM, et al.Amniotic membrane graft to conjunctival flap in treatment of non-viral resistant infectious keratitis: A randomised clinical study. Br J Ophthalmol, 2015; 99(1):59–63; doi: 10.1136/bjophthalmol-2014-305224
10.
ZhuS, YinJ, SinghRB, et al.Use of cyanoacrylate glue in corneal thinning and perforation associated with infectious keratitis. Invest Ophthalm Vis Sci, 2019; 60(9):3231.
11.
SinghRB, ZhuS, YungA, et al.Efficacy of cyanoacrylate tissue adhesive in the management of corneal thinning and perforation due to microbial keratitis. Ocul Surf, 2020; 18(4):795–800; doi: 10.1016/j.jtos.2020.08.001
12.
SharmaN, SahayP, MaharanaPK, et al.Management algorithm for fungal keratitis: The TST (Topical, Systemic, and Targeted Therapy) protocol. Cornea, 2019; 38(2):141–145; doi: 10.1097/ICO.0000000000001781
13.
DasAV, ChaurasiaS, JosephJ, et al.Clinical profile and microbiological trends of therapeutic keratoplasty at a network of tertiary care ophthalmology centers in India. Int Ophthalmol, 2022; 42(5):1391–1399; doi: 10.1007/s10792-021-02127-y
14.
NaranjoA, ArboledaA, MartinezJD, et al.Rose bengal photodynamic antimicrobial therapy for patients with progressive infectious keratitis: A pilot clinical study. Am J Ophthalmol, 2019; 208:387–396; doi: 10.1016/j.ajo.2019.08.027
15.
FernandesM, ViraD, MedikondaR, et al.Extensively and pan-drug resistant Pseudomonas aeruginosa keratitis: Clinical features, risk factors, and outcome. Graefes Arch Clin Exp Ophthalmol, 2016; 254(2):315–322; doi: 10.1007/s00417-015-3208-7
16.
de Paiva A deCM, Ferreira M daC, da Fonseca A deS. Photodynamic therapy for treatment of bacterial keratitis. Photodiagnosis Photodyn Ther, 2022; 37:102717; doi: 10.1016/j.pdpdt.2022.102717
17.
GargP, DasS, RoyA. Collagen cross-linking for microbial keratitis. Middle East Afr J Ophthalmol, 2017; 24(1):18–23; doi: 10.4103/meajo.MEAJO_305_16
18.
PrajnaNV, RadhakrishnanN, LalithaP, et al.Cross-Linking Assisted Infection Reduction (CLAIR): A randomized clinical trial evaluating the effect of adjuvant cross-linking on microbiological and clinical outcomes in fungal keratitis. Ophthalmology, 2020; 127(2):159–166; doi: 10.1016/j.ophtha.2019.08.029
19.
AmescuaG, ArboledaA, NikpoorN, et al.Rose bengal photodynamic antimicrobial therapy: A novel treatment for resistant fusarium keratitis. Cornea, 2017; 36(9):1141–1144; doi: 10.1097/ICO.0000000000001265
20.
MartinezJD, ArrietaE, NaranjoA, et al.Rose bengal photodynamic antimicrobial therapy: A pilot safety study. Cornea, 2021; 40(8):1036–1043; doi: 10.1097/ICO.0000000000002717
21.
BaggaB, SharmaS, AhirwarLK, et al.Clinical outcomes of rose bengal mediated photodynamic antimicrobial therapy on fungal keratitis with their microbiological and pathological correlation. Curr Eye Res, 2022; 47(7):987–994; doi: 10.1080/02713683.2022.2058019
22.
Sepulveda-BeltranPA, LevineH, AltamiranoDS, et al.Rose bengal photodynamic antimicrobial therapy: A review of the intermediate-term clinical and surgical outcomes. Am J Ophthalmol, 2022; 243:125–134; doi: 10.1016/j.ajo.2022.08.004
ZhuH, AltC, WebbRH, et al.Corneal crosslinking with rose bengal and green light: Efficacy and safety evaluation. Cornea, 2016; 35(9):1234–1241; doi: 10.1097/ICO.0000000000000916
25.
Khan-LimD, BerryM. Still confused about rose Bengal? Curr Eye Res, 2004; 29(4–5):311–317; doi: 10.1080/02713680490516864
26.
DaiT, FuchsBB, ColemanJJ, et al.Concepts and principles of photodynamic therapy as an alternative antifungal discovery platform. Front Microbiol, 2012; 3:120; doi: 10.3389/fmicb.2012.00120
27.
PrzygodaM, Bartusik-AebisherD, DynarowiczK, et al.Cellular mechanisms of singlet oxygen in photodynamic therapy. Int J Mol Sci, 2023; 24(23):16890; doi: 10.3390/ijms242316890
28.
SaiDL, LeeJ, NguyenDL, et al.Tailoring photosensitive ROS for advanced photodynamic therapy. Exp Mol Med, 2021; 53(4):495–504; doi: 10.1038/s12276-021-00599-7
29.
HungJH, LeeCN, HsuHW, et al.Recent advances in photodynamic therapy against fungal keratitis. Pharmaceutics, 2021; 13(12):2011; doi: 10.3390/pharmaceutics13122011
30.
LambertCR, KochevarIE. Electron transfer quenching of the rose Bengal triplet state. Photochem Photobiol, 1997; 66(1):15–25; doi: 10.1111/j.1751-1097.1997.tb03133.x
31.
ValenzenoDP, TrudgenJ, HutzenbuhlerA, et al.Singlet oxygen involvement in photohemolysis sensitized by merocyanine-540 and rose bengal. Photochem Photobiol, 1987; 46(6):985–990; doi: 10.1111/j.1751-1097.1987.tb04881.x
32.
AllenMT, LynchM, LagosA, et al.A wavelength dependent mechanism for rose bengal-sensitized photoinhibition of red cell acetylcholinesterase. Biochim Biophys Acta, 1991; 1075(1):42–49; doi: 10.1016/0304-4165(91)90072-o
33.
KharkwalGB, SharmaSK, HuangY-Y, et al.Photodynamic therapy for infections: Clinical applications. Lasers Surg Med, 2011; 43(7):755–767; doi: 10.1002/lsm.21080
34.
HaliliF, ArboledaA, DurkeeH, et al.Rose bengal- and riboflavin-mediated photodynamic therapy to inhibit methicillin-resistant staphylococcus aureus keratitis isolates. Am J Ophthalmol, 2016; 166:194–202; doi: 10.1016/j.ajo.2016.03.014
35.
ArboledaA, MillerD, CabotF, et al.Assessment of rose bengal versus riboflavin photodynamic therapy for inhibition of fungal keratitis isolates. Am J Ophthalmol, 2014; 158(1):64–70.e2; doi: 10.1016/j.ajo.2014.04.007
36.
CherfanD, VerterEE, MelkiS, et al.Collagen cross-linking using rose bengal and green light to increase corneal stiffness. Invest Ophthalmol Vis Sci, 2013; 54(5):3426–3433; doi: 10.1167/iovs.12-11509
37.
KochevarIE, ZhuH, AltC, et al.Crosslinking corneal collagen in vivo using rose bengal and green light. Invest Ophthalmol Vis Sci, 2014; 55(13):2988.
38.
SinghM, LiJ, HanZ, et al.Evaluating the effects of riboflavin/UV-A and rose-bengal/green light cross-linking of the rabbit cornea by noncontact optical coherence elastography. Invest Ophthalmol Vis Sci, 2016; 57(9):OCT112–OCT120; doi: 10.1167/iovs.15-18888
39.
NaranjoA, PelaezD, ArrietaE, et al.Cellular and molecular assessment of rose bengal photodynamic antimicrobial therapy on keratocytes, corneal endothelium and limbal stem cell niche. Exp Eye Res, 2019; 188:107808; doi: 10.1016/j.exer.2019.107808
40.
ChenJ, LaiJ, Navia VelasquezJC, et al.Rose Bengal penetration depth with iontophoresis in human cornea tissue. Invest Ophthalmol Vis Sci, 2023; 64(8):4027.
41.
AydemirME, HafeziNL, LuNJ, et al.Combining riboflavin/UV-A light and rose Bengal/green light corneal cross-linking increases the resistance of corneal enzymatic digestion. Transl Vis Sci Technol, 2024; 13(1):30; doi: 10.1167/tvst.13.1.30
42.
FadlallahA, ZhuH, ArafatS, et al.Corneal resistance to keratolysis after collagen crosslinking with rose Bengal and green light. Invest Ophthalmol Vis Sci, 2016; 57(15):6610–6614; doi: 10.1167/iovs.15-18764
43.
LaiJM, ChenJ, NaviaJC, et al.Enhancing rose Bengal penetration in ex vivo human corneas using iontophoresis. Ther Deliv, 2024; 15(8):567–575; doi: 10.1080/20415990.2024.2371778
44.
Tefon AribaşAB, SarikayaB, BilgihanK. Iontophoresis-Assisted rose Bengal and green light corneal cross-linking. Cornea, 2020; 39(12):1533–1540; doi: 10.1097/ICO.0000000000002494
45.
NakonechnyF, NisnevitchM, NitzanY, et al.Sonodynamic excitation of rose Bengal for eradication of gram-positive and gram-negative bacteria. Biomed Res Int, 2013; 2013:684930; doi: 10.1155/2013/684930
46.
ChenHJ, ZhouXB, WangAL, et al.Synthesis and biological characterization of novel rose Bengal derivatives with improved amphiphilicity for sono-photodynamic therapy. Eur J Med Chem, 2018; 145:86–95; doi: 10.1016/j.ejmech.2017.12.091
47.
WenX, ZhangX, SzewczykG, et al.Potassium iodide potentiates antimicrobial photodynamic inactivation mediated by rose Bengal in in vitro and in vivo studies. Antimicrob Agents Chemother, 2017; 61(7); doi: 10.1128/aac.00467-17
48.
PlanasO, MaciaN, AgutM, et al.Distance-Dependent plasmon-enhanced singlet oxygen production and emission for bacterial inactivation. J Am Chem Soc, 2016; 138(8):2762–2768; doi: 10.1021/jacs.5b12704
49.
KustovA, MorshnevP, KukushkinaN, et al.The effect of molecular structure of chlorin photosensitizers on photo-bleaching of 1,3-diphenylisobenzofuran—the possible evidence of iodine reactive species formation. Comptes Rendus Chimie, 2022; 25(G1):97–102; doi: 10.5802/crchim.158
50.
WeiD, HamblinMR, WangH, et al.Rose Bengal diacetate-mediated antimicrobial photodynamic inactivation: Potentiation by potassium iodide and acceleration of wound healing in MRSA-infected diabetic mice. BMC Microbiol, 2024; 24(1):246; doi: 10.1186/s12866-024-03401-6
51.
El-KholyAI, Abdel FadeelD, NasrM, et al.(Rose bengal)/(Eosin Yellow)-Gold-polypyrrole hybrids: A design for dual photo-active nano-system with ultra-high loading capacity. Drug Des Devel Ther, 2021; 15:5011–5023; doi: 10.2147/DDDT.S338922
52.
GhoniemDF, AbdelkawiSA, FadelM, et al.Novel photodynamic/photothermal treatment of fungal keratitis using rose bengal-loaded polypyrrole-gold nanoparticles in wistar albino rats. J Ocul Pharmacol Ther, 2023; 39(6):379–388; doi: 10.1089/jop.2023.0004
53.
PrajnaN, LalithaP, SharmaS, et al.A double-masked, sham-controlled trial of rose Bengal photodynamic therapy for the treatment of fungal and acanthamoeba keratitis: Rose Bengal Electromagnetic Activation with Green Light for Infection Reduction (REAGIR) study. Trials, 2024; 25(1):566; doi: 10.1186/s13063-024-08376-3
