DOS Times Vol 25 No 5

DOS Executive Members 2017-19

DOS Office Bearers

Dr. Subhash C Dadeya Dr. Pawan Goyal Dr. Namrata Sharma Dr. Hardeep Singh
President Vice President Secretary Joint Secretary

Dr. Jatinder S Bhalla Dr. Vinod Kumar Dr. Manav Deep Singh
Treasurer Editor Library Officer

Executive Members

Dr. Dewang Angmo Dr. Jatinder Bali Dr. Shantanu Gupta Dr. C. P. Khandelwal

Dr. Rahul Mayor Dr. Vipul Nayar Dr. Rajendra Prasad Dr. Kirti Singh

DOS Representative to AIOS Ex-Officio Members

Dr. Jeewan S. Titiyal Dr. M. Vanathi Dr. Rakesh Mahajan Dr. Subhash C Dadeya Dr. Arun Baweja

Contents

Editorial Basics

07 Virtual is the New Normal in Conferences 48 Ocular Changes During Pregnancy
10 Outgoing President’s Address
12 Incoming President’s Address PG Corner
14 Secretary’s Report 2019-2020
52 Limbal Stem Cell Deficiency
Beyond Ophthalmology
Photo Essay
20 Non Antibiotic Antimicrobials for Ocular Infection
59 Highlighting a case of Lipaemia Retinalis in Young
What’s New Diabetic, with Undetected Hyper-Cholesterolaemia

25 Upneeq Monthly Meeting Update

Subspecialities 63 Curls and Curves: A Rare Cause of Vitreous
Haemorrhage
Cornea
66 Anterior Segment Laser Procedures - Preventing
26 Corneal Allogenic Intrastromal Ring Segments Spikes A Journey of Four Studies
(CAIRS) for Treating Keratoconus, other Corneal
Ectasias and Synthetic ICRS Related Melts 70 Brimonidine Induced Bilateral Uveitis and Severe
Ocular Surface Damage in a Patient of Primary
30 Ophthalmia Neonatorum Open Angle Glaucoma: A Case Report and Review of
Literature
Retina
DOS Quiz
35 Neurogenic and Vasculogenic Components in
Diabetic Retinopathy Tearsheet

Oculoplasty 77 Orbital Cellulitis
79 Ocular Surface Neoplasia - Treatment Outcomes
40 Siliconoma of Eyelid Following Intravitreal Silicone
Oil Insertion

Comprehensive Ophthalmology

43 An Overview of Artificial Intelligence in
Ophthalmology

www.dosonline.org/dos-times DOS Times - Volume 25, Number 5, March-April 2020 03

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Volume 25 No. 3, November-December, 2019

Editor In Chief DOS Times Editorial Board
Namrata Sharma
Editorial Board National Board
Editor Dr. Parul Icchpujani
Prafulla Kumar Maharana Dr. Atul Kumar Dr. Ronnie George
Dr. Aniruddha Maiti Dr. Sushmita Kaushik
Assistant Editors Dr. Apporva Ayachit Dr. Gopal Pillai
Dr. Jitendra Jethani Dr. Usha Singh
Ritu Nagpal Siddhi Goel Dr. Mita Joshi Dr. Subhendu Boral
Dr. P. Dutta Majumdar Dr. Meena Chakrabarti
Dr. Noopur Gupta Dr. Raksha Rao
Dr. Brijesh Kakkar Dr. Kumudini Verma
Dr. Digvijay Singh Dr. Rashmin Gandhi
Dr. Ritika Sachdev Dr. Siddharth Kesarwani
Dr. Dewang Angmo Dr. Chaitra Jayadev
Dr. Rebika Dr. Bibhuti P. Sinha
Dr. Saurabh Sawhney Dr. Amit Porwal
Dr. Reena Sharma Dr. Prashant Bawankule
Dr. Rajat Jain Dr. Arvind Kumar Morya
Dr. Jaya Gupta
Deepali Singhal Sahil Agarwal Dr. Anita Ganger
Ritika Mukhija Rahul Kumar Bafna Dr. Umang Mathur
Dr. Neera Agarwal
Farin Shaikh Divya Agarwal Dr. Poonam Jain
Mohamed Ibrahime Asif Venkatesh Nathiya Dr. Manisha Agarwal
Dr. Hardeep Singh
Dr. Anita Sethi
Dr. Tushar Agarwal
Dr. Rohit Saxena
Dr. Swati Phuljhele
Dr. Vivek Dave
Dr. Mohita Sharma
Dr. Rajesh Sinha
Dr. Ritu Arora
Dr. P.K. Pandey
Dr. H.K. Yaduvanshi
Dr. O.P. Anand

Anusha Sachan Abhijeet Beniwal

Gunjan Saluja Akshaya Balaji
www.dosonline.org/dos-times
DOS Times - Volume 25, Number 5, March-April 2020 05

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Editorial

From the
Editor Desk

Virtual is the New Normal in Conferences

Respected Seniors and Friends,

With the advent of ongoing successful webinars, the new normal in conferences has been
upgraded to virtual. World Ophthalmology Congress which was held virtually in the month of
June this year was attended by over 7000 ophthalmologists from all over the world. Likewise,
recently American Academy of Ophthalmology has also announced about going virtual. Thus,
this year for conferences the virtual will be the new normal. Although this is being done per
force due to corona virus yet it comes with several advantages.

Conferences can be held at anytime, from any location with an adequate internet facility. It
takes only seconds to connect and brings the audience together on a single platform in no time.
With ongoing technologies they can be easily arranged via online websites.

Using virtual conferences saves a huge bulk of money in travel expenses, accommodation,
catering, auditorium and lost time from work. It allows people to connect from around the
globe without travelling to a distant location.

Morover, the sessions can be recorded and reviewed after cessation the conference by the
audience. This comes handy to the postgraduates and fellows for learning difficult concepts
and also provides an opportunity of note taking when viewed in an offline mode later. Prof. (Dr.) Namrata Sharma

Exceptionally high number of international delegates and faculty can be made virtually (MD, DNB, MNAMS)
available who otherwise would not have attended the physical conference due to long distance
travel issues and financial constraints. Thus it has become convenient to interact with the Hony. General Secretary
international faculty from various continents such as Europe, America, Africa etc. Delhi Ophthalmological Society
Whiteboard features enable drawing and typing on the screen to enable sketch type
illustrations of ideas and capture of notes. Text chatting features enable easy question and Cornea, Cataract & Refractive Surgery Services
answer interaction, surveys, polls, sharing of website addresses and other information in real Dr. R.P. Centre for Ophthalmic Sciences,
time. All India Institute of Medical Sciences (AIIMS)
New Delhi

It is not always possible to attend every meeting you receive an invite for. Virtual meetings give people the opportunity to attend from their
workspace. They are also a quicker and efficient way to coordinate and conduct urgent meetings.

Since virtual systems work on green technology and also reduces travel and paper printing, it can reduce the increasing amount of carbon in
the environment.

However, virtual platform come with a handful of drawbacks as well. People have a greater opportunity to multi-task when they are involved
in a virtual meeting. They may become distracted with attending phone calls, answering to messages, network and audio issues. It is more
difficult to stay engaged in an online discussion.

Necessary equipments are required for virtual meetings such as the proper hardware, software and 4G internet connection. They will also
need to be properly trained. A lack of coordination on any of these issues will undermine the success of a virtual meeting.

Of late there have been many reports of eyestrain and headache at the end of the day leading to reduced productivity and refraining oneself
from attending further virtual conferences.

The virtual meeting does not appeal to everyone from a cultural standpoint. Many older generation physicians are uncomfortable with new
technology, especially if they have been accustomed to physical lectures and conferences.

Face to face meeting and interaction is not possible with the mentors. Usually, when the residents or fellows travelling from far flung areas
attend conferences in countries like America and Europe, they club their conference visit with their visit to the centre of excellence in
ophthalmology which possibly cannot happen now.

Social networking is not possible. There may be higher rates of registrations with no show due to loss of interest or some other preoccupation.

As most of the attendees straight away logout as soon as the moderators or panellists commence with their closing statements, collecting
feedback remains a major issue.

This year for DOS annual 2020 we will have to take a call as to how to do the conference. We did a virtual General Body Meeting dated 17th
May, 2020 as we had constitutional responsibility. Very soon we will have to decide about annual DOS conference. Please do think about it
and let me know your thoughts on it.

With best wishes.

Prof. (Dr.) Namrata Sharma

(MD, DNB, MNAMS)

Hony. General Secretary
Delhi Ophthalmological Society

www.dosonline.org/dos-times DOS Times - Volume 25, Number 5, March-April 2020 07



From President’s Desk

Dear friends and colleagues,
Greetings from DOS.
The Aim of DOS times is to provide platform to authors as well as Residents to
publish Scientific papers of rich and diverse academic content.
We begin as new team ,but strive towards academic excellence, the ultimate
goal of DOS. In coming one year ,we will attempt to extend and spearhead this
educational brilliance through various issues of DOS times.
Let us all aim to work towards our objective to promote healthy teaching,surgical
skill transfers,ethical conduct and state of art cutting edge technology.
I would like to congratulate our Dynamic Secretary and Editor in chief DOS
times Prof Namrata Sharma and entire editorial team and authors for bringing an
Excellent issue of DOS times covering topics of prime importance.
We will continue with various other academic activities e.g Monthly clinical meetings,Webinars,printing of CME
on common Ophthalmic problems, PG teaching programs, Quiz skill transfer courses,providing online teaching
material,Mid term ,Annual and I DOS conferences.The details will be communicated shortly in due course of time.
I take this opportunity to invite you all to attend First Monthly meeting of this year at GNEC on 30th August 2020.
Happy reading.

(Prof Subhash Dadeya)
Director Prof. Ophthalmology,
Guru Nanak Eye Centre,
Maulana Azad Medical College,
New Delhi.

www.dosonline.org/dos-times DOS Times - Volume 25, Number 5, March-April 2020 09

Outgoing President’s Address

Respected Seniors and Dear Friends,
As your outgoing president, I want to thank you for the privilege of allowing
me to represent you this past year. As president, one gets the opportunity to
express your ideas and beliefs in a way that is valued, respected and can be
heard all across the society. I have sought to speak for all of us to the best of my
ability, and I hope I have accomplished that to your satisfaction. I have tried
to be that one voice that has been consistent on the values and principles that
have help us reach where we are today.
For me it was a golden year with nostalgic memories since I took over the
prestigious post of pres-ident DOS. During this year executive committee
strived hard to achieve new heights which was visible at various platforms:
• Mid-term conference was a huge all-round success with great academics

and high on attendance and hospitality.
• Monthly clinical meets organised by respective institutions were well

appreciated. Here, I want to make special mention of the last monthly meet organised by the Centre for sight
which was first virtual monthly meet under the aegis of DOS. Dr. Mahipal deserves a huge applause for this initi-
ative.
• We take pride in announcing that we enrolled more than 260 members to the DOS family in this last year. Though
it was a joint effort of all executive members but Dr Bhalla needs special men-tion for his untiring efforts in this
endeavour.
• We had a successful DOS teaching programme with AIOS and eye donation awareness program with NPCB
at RPC, AIIMS .This was possible only with help of Chief Dr. RP Centre Professor Atul Kumar who is always
supportive for the DOS activities.
• Glaucoma awareness program conducted with Govt of India at RML hospital which was coordi-nated by Dr M D
Singh, DOS library officer, deserves applause.
• Sports day along with family picnic organised in March was one of its kind, with an exciting crick-et match,
badminton, table tennis, magic show and an afternoon full of fun, food and frolic. Dr Jatinder Bali and Dr Shantanu
deserve a special mention for the success of sports day.
There were many other activities which were detailed in the secretary report.
We wanted to continue this saga of successful stories by holding I-DOS and Annual Dos confer-ence. However, we fell
prey to the calamity of Corona which struck the world and all our further activities.
Annual DOS conference for now stands postponed, however, we have full intentions of holding it in full vigour as and
when the situation improves. We are also speculating the prospect of virtual or hybrid conference in case of delayed
recovery of the current situation.
My speech and tenure would be incomplete without mention and support of my very hard working executive and
very talented Secretary Dr Namrata Sharma and treasurer Dr JS Bhalla for standing with me during this year always
and bringing laurels to DOS. No society can run smoothly without the support of its staff who work behind the scenes
but hold the key to success of each and every event. My heartfelt thanks to all my DOS staff.

10 DOS Times - Volume 25, Number 5, March-April 2020 www.dosonline.org/dos-times

When an individual is on centre stage, it is only because of unrelentless support of his family members, and all words
will fail short of expressing my gratitude to them.
I seek forgiveness for any omission of my duties at any point during my tenure.
I also take this opportunity to welcome the incoming president Dr Subhash Dadeya. I would like to suggest the
incoming president to explore the option of online DOS election if the present situation continues longer, so that the
society continues to function smoothly according to the norms of DOS constitution.

We as responsible Doctors, as Society or for that matter as Citizen of this great country are never better till we are
tested just as in this current situation. Guidelines will keep evolving as situations keep on changing. We must also
change for better with time as individuals and collectively as our beloved DOS.

LONG LIVE DOS.

With Best Regards
Dr. Rakesh Mahajan
President DOS 2019-2020

www.dosonline.org/dos-times DOS Times - Volume 25, Number 5, March-April 2020 11

Incoming President’s Address 2020-2021

Dr Rakesh Mahajan, Immediate Past President DOS, Dr Namrata Sharma
Secretary DOS, Dr JS Bhalla Treasurer DOS, All the office bearers and members
of Executive DOS, All past Presidents and past office bearers of DOS, my
respected teachers, seniors, Dear Friends and fellow Ophthalmologists
Greetings and Good Afternoon to one and all.
Warm Welcome to each one of you to the Virtual GBM.
At the outset, I would like to thank each one of you for the confidence that you
have shown in electing me Vice President last year.
It is great honour to be following in the footsteps of great Presidents of Society,
All of whom have made a significant contribution to the Society.
I have the privilege to have interacted with most of them on one or other
occassion.
I hope that some of their dedication, wisdom and good humour has passed on to me to allow to me to carry out the
task in a positive and productive manner. I salute all of them.
I thanks one and all for the utmost cooperation I received from all of you during my tenure as Vice President, Secretary,
Library officer and executive of the DOS.
When I took over as Secretary DOS, three years back I have imagined and reimaigned what is an ideal DOS.I prepared
a roadmap for a vibrant DOS committed to academic excellence, concerns of common members, financially
independent and transparent organisation,
Whatever was promised, more than that was delivered.
Now, it is the turn of completing other important tasks, which are vital for the Society.
In addition to routine activities of DOS, We should specially focus on the issues related to Constitutional amendments,
DOS house, Day care centre act, various issues related to renewal of registrations, TPA. Coronarelated issue, central act
for violence against doctors, online voting, and issue of CHS rates and Harrassment of common members.
The Various routine activities like monthly meeting, evening CME, Webinars, Printing of CME on common
Ophthalmic problems,
Mid-term, Annual and I DOS conference, PG teaching, Annual get together, Charitable activities, DOS Picnic, Cricket
match, Sub speciality skill transfers, provision of online journals and awareness program will continue.
All other common members friendly initiatives will continue.
Let us ensure DOS grows from strength to strength and scales greater heights committed to academic excellence.
I aims to fulfill the aspirations of common members for which DOS was founded for, reform our existing norms,
provide you with best of bests and ensure transparency.

12 DOS Times - Volume 25, Number 5, March-April 2020 www.dosonline.org/dos-times

Let us Make a New start and move forward to meet the great challenges,we face.
Let us rise as one to meet these challenges of tying time so that future generations might thank us and say that that
was the finest time of DOS.
Therefore, I ask for your help and support as always ,because it is with your cooperation that I have managed to
achieve whatever little that I have.
The affection and regards that I have received from all of you gives me courage to stand up for our collective rights
and responsibilities.
I look forward to our continued association. please send your suggestions and inputs by email to me at dadeya868@
gmail.com or by what’s app at 9810575899.
Before, I conclude, I thank almighty, who has always been very kind to me.
I would like to convey my gratitude to my all respected teachers and seniors and colleagues.
I would like to thank all my supporters and assure them, I will not let you down and will keep on working for common
members as I Do not have fear of missing out.
I would like to thank Worthy Dean MAMC Prof Sushil Kumar sir and Ld Director GNEC Prof Ritu Arora, for providing
the atmosphere of academic excellence.
Thanks to all faculty, residents and Staff of my institution for constant support.
I am indebted to my lovely family, whose support is backbone for the positive energy for every task.
Once again thank you all for giving me the opportunity and responsibility.
Please take care, stay safe and healthy.
Long live DOS.

With best Regards
Prof Subhash Dadeya
President DOS 2020 -2021

www.dosonline.org/dos-times DOS Times - Volume 25, Number 5, March-April 2020 13

Secretary’s Report – 2019-2020

Obituary References (2019-2020)
With profound grief we inform the sad demise of
Dr. A.C. Chadha (Past President – DOS)
who left for heavenly abode on 07 January 2020
(29 July 1932 - 7 January 2020)

Dr. Santosh Chaudhry
who left for heavenly abode on 08 January 2020
(05 March 1957 - 8 January 2020)
Honorable President, Dr. Rakesh Mahajan, Incoming President Dr. Subhash
Dadeya, respected Senior Members of the society and my dear friends I
welcome you all to this General Body Meeting of the Delhi Ophthalmological
Society for the year 2019-2020.
On behalf of the executive committee, it is my pleasure and privilege to extend a warm welcome to everyone in this
General Body Meeting. For the first time, we are organizing an online GBM due to CVOID 19 outbreak which is there
throughout the entire world.
I wish to express my sincere gratitude and appreciation to all the members of the entire executive committee and all
the members of DOS for extending overwhelming support and encouragement throughout this current academic
year. The DOS Executive has been constantly striving hard to take DOS to greater heights and set higher standards in
all its activities.
DOS Membership: DOS is the world’s largest state ophthalmological society with its current membership of 9730
members. We are happy to announce an addition of 261 new members to our society and extend a warm welcome to
them.
2019-2020
Delhi : 66
Outside : 195
Total : 261
DOS Monthly Clinical Meetings
There were 9 DOS monthly clinical meetings which were held between July 2019 and March 2020. The last physical
meeting was held at Dr. RML Hospital which was also made live on face book. For the first time in the history of DOS,
monthly virtual meeting was held on the 10th March 2020 from Centre for Sight between 11:00 am to 1:00 pm. This
was done after due recommendation from the executive that since it was not possible to hold it physically, this may
be done virtually. This was made face book live and You tube live and was viewed by a large number of DOS members.
Overall all monthly meetings have been successful.
DOS Subspecialty Meetings & other events
1. For the first time, DOS – AIOS collaboration was done the Delhi ophthalmological society Teaching Programme:

Education @ Dr. R.P. Centre; this was organized at Dr. R.P. Centre and India Habitat Centre from 4-6th October

14 DOS Times - Volume 25, Number 5, March-April 2020 www.dosonline.org/dos-times

2019. This program consisted of interactive sessions and visit at the various investigation labs at Dr. R.P. Centre
and also the didactic teaching with hands on at India Habitat Centre.
2. Workshop was conducted by CA & GST Experts on 23.8.19 from 2- 4 pm at DDU Hospital to apprise our members
about the GST issues; this was organized by Dr. J.S. Bhalla with a very good response.
3. DOS Picnic & Cricket Match was organized in Khel Parisar on 1st March 2020 (Sunday) which was enjoyed by one
and all. Again, my special thanks to Dr. Jatinder Bali, Dr. Shantanu Gupta and Dr. Rahul Mayor along with the
President Dr. Rakesh Mahajan for organizing this.
4. CME was organized on “Tomography meets biomechanics” on the 8th December 2019 at India Habitat Centre in
which Dr. Vishal Jhanji participated from Pittsburgh, USA along with the esteemed national faculty from Delhi.
This was attended by over 250 DOS members
5. DOS also organized the Walk for 34th Eye Donation Awareness in conjunction with National Eye Bank Dr. R.P.
Centre on 3rd September 2019, which had wide participation and support from DOS members.
6. DOS Webinars: Successful webinars were organized on different subspecialties in DOS which are as follows:
1. Webinar on “Keratoconus “Answer your questions on 16th May ,2020
2. Webinar on “Burning issues facing the Ophthalmic Community” Wednesday, 13th May 2020,
3. Webinar on “Modern Day Lens Extraction Technologies” Tuesday, 12th May 2020
7. Webinar on Astigmatism Management, Friday, 8th May 2020
8. Webinar on “GLAUCOMA BASICS”, Tuesday, 5th May 2020
9. Webinar on “Being “Tech Savvy” in Ophthalmology, Saturday, 2nd May 2020,
10. Webinar on “Evolution from COVID to post COVID Era -Impact on our Profession”, 22nd April 2020,
11. Webinar on “Trifocal IOL”, 20 April 2020
12. Webinar on “Why MGD matters and How Vector Thermal Pulsation Helps?” 15th April 2020

World Glaucoma Week 2020
World Glaucoma Week was observed by several of our members between 8th March to 14th March 2020.The theme
this year is “Beat Invisible Glaucoma.” A program which was organized by Dr. Manavdeep Singh, was held for public
awareness of glaucoma on 11.3.2020 at Dr. RML Hospital. This was the combined effort with MOHFW, Dr RML
Hospital, Glaucoma Society of India (GSI), All India Ophthalmological Society (AIOS) and Delhi Ophthalmological
Society (DOS). The event was also transmitted live to 100 Medical Colleges through National Medical College Network.
A movie for public on glaucoma education was also unveiled at this event. There was press coverage of this event and
it was widely appreciated.

DOS Times 2019 - 2020
The cover page of the DOS Times was changed which was much appreciated. The quality of the paper as well as
printing was improved with all color pages. This year the postal delivery of DOS Times was clubbed with the DJO to
save costs. The last issue of DOS times and DJO were sent online due to lockdown in the country. One whole issue was
dedicated to CORONA related information.

DOS website (www.dosonline.org)
A completely new website has been launched and revamped with the address: dosonline.org. DOS has made new
official ids for all the office bearers so that now everyone can communicate with the same rather than their personal
IDs. This will also be of help as the office bearers change every two years. There are other features which have been
added.

1. The members can update their profile on their own online.
2. DOS Times has been made as e-book format / flip book to improve readability.

www.dosonline.org/dos-times DOS Times - Volume 25, Number 5, March-April 2020 15

3. Member Directory has been updated.
4. Articles are now being submitted online on the submission portal rather than on the email.
5. International News in Ophthalmology corner has been added.
6. IDOS, Winter Conference & Annual Conference are now on a single platform rather than multiple websites.
DOS website & mobile app have been launched with new sophisticated outlook with all its upgraded and user-friendly
navigation options.

DOS Library
DOS library is a popular service providing excellent academic resource materials to the ophthalmologists across
the country. Since the policy of OVID changed and it gave only one IP address per user, M/s Sun Pharmaceuticals
Company was approached who is now providing 6 online journals and 20 books (List available at Website) on our IP
address free of cost for the period of one year from Ovid.

A. Six Journals include
1. Cornea
2. Current Opinion in ophthalmology
3. International Ophthalmology Clinics
4. Journal of Glaucoma
5. Retina
6. RETINAL Cases & Brief Reports

There is availability of 83 journals, guidelines, clinical trials, teaching videos, grand rounds, and slides and much more
under academic material at DOS website.

The details report will be read by Dr. Manav Deep Singh Library officer.

Winter DOS Conference 2019
The Delhi Ophthalmological Society organized a very successful DOS Winter Conference with the theme of “Inspire
& Innovate” on 2nd & 3rd November 2019, at Ashok Hotel, New Delhi. This conference brought together clinicians,
researchers and educators from India and abroad. It put on display a plethora of state of art ophthalmic academic
work, surgical demonstrations, lively debates, interactive symposia and ophthalmic quiz.

71st Annual Conference of DOS –2020: Ophthalmology in 2020 and beyond.

The 71st Annual Conference of Delhi Ophthalmological Society, New Delhi was to be organized at the Hotel Ashok,
Chanakyapuri, New Delhi from 3rd to 5th April 2020. However due to the ongoing COVID 19 pandemic situation in
India as well as in the entire world, we tentatively blocked the following dates which were as follows:

1. 29th to 31st May 2020
2. 5th to 7th June 2020
3. 26th to 28th June 2020
4. 19th to 21st June 2020
5. 14th to 16th August 2020
A decision on whether a virtual or hybrid or physical conference will take place will be decided in the 1st week of
August as per the decision of the executive committee. Dr Subhash Dadeya agreed in the executive committee meeting
that since the annual DOS conference 2020 could not be held physically, whenever it is held in future (physical or
virtual), it will be held under the chairmanship of Dr Mahajan. A decision will be taken that we may have to hold a
virtual / physical / hybrid annual DOS conference 2020 at a later date.

16 DOS Times - Volume 25, Number 5, March-April 2020 www.dosonline.org/dos-times

DOS House
The proposal of DOS house was deferred in view of the fluid financial situation in COVID 19 times by the executive
committee.

DOS Membership Drive
The DOS membership drive was successfully undertaken by Dr. J.S. Bhalla for several benefits which were extended to
residents to encourage them to become DOS Members.

The I-DOS Conference 2020
The International-DOS Conference 2020 was to be held at Bhutan from 18th -21st March, 2020 was postponed due to
COVID 19 Pandemic.

Income Tax notice to DOS
Income tax notice / scrutiny was received for the Assessment year 2017-18 and was amicably resolved. We thank Dr
Pawan Goyal in helping with this.

PIL on TPA issue
The PIL on TPA issue is under jurisdiction and the next date of hearing is 19th June 2020.

Constitutional amendment
Dr O.P. Anand, Ex-Chairman of DOS Constitutional Committee presented the report of DOS Constitution to the
executive committee. Dr. O.P. Anand said that he had modified the submitted constitution further. He handed over
the revised constitution to the President, DOS Dr. Rakesh Mahajan.

In Reference to NOC of Fire Clearance Certificate from Fire Services Department by the DOS members, several
communications have been sent to the following.

1. Director, Health Services,
2. Letter to DGHS, Government of Delhi
3. Letter to Lieutenant Governor, Government of Delhi
4. Directorate of Health Services, Government of Delhi for show cause notice
5. Letter to Deputy Chief Fire Officer, Government of Delhi
During the COVID 19 pandemic, several relief measures were followed up by the secretariat. This was in relation to
the following:

1. Subsidence of the salaries of Healthcare Staff
2. Provision for compensation to the medical professionals and workers for disease contracted during patient care
3. Interest free loans to Healthcare providers for the next one year.
4. Releasing PSU payments (CGHS, ECHS etc.) and TPA payments of Government Insurance Companies for services

rendered by the hospitals, at the earliest.
5. Moratorium on statutory dues
6. Temporary stoppage on EMI payments and interest.
7. Subsidy on Electricity and Water Bills of medical establishments.
8. Waiving off Corporation Taxes
9. Freezing Rental dues & utility payments

www.dosonline.org/dos-times DOS Times - Volume 25, Number 5, March-April 2020 17

10. Immediate rectification and relief in Advance Tax
11. Allowing input credits for GST
12. All accreditations and registrations to be valid till after the crisis is over.
With effect to the above the letters were posted to the following:

1. Sh. Anil Baijal, Lieutenant Governor
2. Dr. Harsh Vardhan, Minister of Health and Family Welfare
3. Ms Nirmala Sitharaman, Hon’ble Minister of Finance
4. Dr. Satinder Jain, Health Minister, GOVT of NCT,
5. Sh. Manish Sisodia, Hon’ble Dy. Chief Minister, Finance Department Government of NCT of Delhi
Further various COVID -19: DOS initiatives were taken which included the followed

1. Special Edition: The 2020 Pandemic COVID-19 by Dr. Dewang Angmo
2. Write up of Brief Overview by Dr. Jatinder Bali and Dr. Kirti Singh
3. Special edition on Corona Times with guest editorial by Dr. J.S. Bhalla
To expedite applications for new registration, DOS sent the representation and communication to Dr. R.N. Das
regarding renewal of registration of Nursing homes.

PPE Kits: The DOS Secretariat has arranged a sponsor who has agreed to donate 15000 PPE Kits , which will be
distributed across various hospitals in Delhi and also to the DOS members. Thanks to the president, Dr. Rakesh
Mahajan for helping with the logistics of the same.

Acknowledgements
I acknowledge the tremendous amount of support extended to DOS by Dr. R.P. Centre for Ophthalmic Sciences, all the
faculty and residents for all academic activities of DOS. My sincere gratitude goes out to the Chief, Prof. Atul Kumar
for providing all infrastructure support to house the DOS office.

I am blessed to be working under the able guidance of our most humble president Dr Rakesh Mahajan, who has
always stood by me and has been very encouraging and supportive and advised me timely on various issues, thank
you Sir for always being there.

Our Treasurer Dr J.S. Bhalla, has been most cooperative and has worked shoulder to shoulder with me in all endeavors.
He has been a pillar of strength and always been there.

I thank Dr Hardeep Singh for filling in my shoes whenever required and for his unclenching support.

I thank all the members of the executive, who have stood by me and supported me in all the activities and all the
members of DOS who have provided invaluable inputs to improve the working culture of the society and participated
in in all the academic initiatives of this executive.

The diligence and hard work of the DOS office staff particularly Mr Parveen Kumar is remarkable. His meticulous
execution and mastery in secretarial assistance skills deserves a special mention.

Mr Sandeep is our hard working and committed accountant, who has worked tirelessly under the able guidance of Dr
J.S. Bhalla our treasurer to keep all accounts in order.

Mr Sunil, our editorial assistant coordinates the typesetting of DOS times as well as the conference related documents.

Mr. Manish, our editorial assistant helps in typesetting of DJO and assists Editor DJO Dr. Vinod Kumar.

18 DOS Times - Volume 25, Number 5, March-April 2020 www.dosonline.org/dos-times

Mr Babu our library staff, assists Dr Manav Deep Singh in DOS library maintenance with dedication and sincerity. Mr
Harshpal our office attendant, is multipurpose worker and is diligent about his duties.
I would like to thank all the members of the executive who have stood by me and supported me in all the activities
and all the members of DOS who have provided invaluable inputs to improve the working of the society.
I would be failing in my duty, if I do not thank my family members for allowing me time away from them to pursue
my endeavors.
Let us work together for taking DOS to glorious heights with sincerity, dedication and commitments
Thanking you once again
Yours sincerely

Prof. Namrata Sharma
Secretary, DOS
2019-2021

www.dosonline.org/dos-times DOS Times - Volume 25, Number 5, March-April 2020 19

Beyond Ophthalmology

Non Antibiotic Antimicrobials for
Ocular Infection

Jatinder Singh Bhalla MS, DNB, MNAMS, Mohmad Uzair MS, Amit Mehtani MS, DNB
Department of Ophthalmology, Deen Dayal Upadhyay Hospital, New Delhi, India.

Abstract: Povidone– iodine (PVI) is a disinfectant and antiseptic agent used for preoperative preparation of the skin and mucous
membranes, as well as for the treatment of contaminated wounds. Preparation of the eyelids, eyelashes, and conjunctiva prior to
intraocular surgery decreases the risk of endophthalmitis. Now, coming to the efficacy of povidone iodine treatment in SARS-
CoV, treatment with povidone iodine for 2 min reduces viral infectivity to below detectable level and the efficiency of povidone
iodine was similar to 70% ethanol in terms of reducing viral infectivity. High concentrations of, and increased contact time
with, povidone-iodine can also oxidize and damage both corneal and conjunctival proteins.
A new therapeutic approach for the treatment of blepharitis is the use of stabilized hypochlorous acid (HOCl). Beyond
blepharitis, it is possible that hypochlorous acid could be used for prophylaxis prior to ocular surgeries and as an alternative or
in addition to other anti-infective agents such as povidone-iodine.

Intraocular postoperative infections used routinely in neonatal conjunctiva. water before drinking also became
are a permanent concern for every Antiseptics and preservatives fall under common practice around this time,
eye surgeon. Although postoperative the umbrella of biocides, which also although heat sterilization was not
endophthalmitis is infrequent, with includes disinfectants (agents used on widespread until after the discoveries of
an incidence rate of 0.06% to 0.09% nonliving surfaces). Antiseptics, which Louis Pasteur in the 18th century.
in the last decade,1-7 it represents are bactericidal, are used to prevent Records from the 4th century indicate
a devastating complication in sepsis through decreasing the bacterial the use of mercury by Arab physicians
ophthalmic surgery. For this reason, the load, while bacteriostatic preservatives as an antiseptic-until its toxic effects
search for optimal procedures that will are used to prevent bacterial growth. were realized. Throughout the
help reduce its incidence is a constant Some biocides, such as povidone- centuries, people discovered the
challenge. Although the incidence iodine, have crossover capabilities antiseptic properties of silver, copper
ofpostoperative infections has a low and have wide applications and high and zinc. The bleaching powers of
rate, an increasing number of cases degrees of efficacy. There is a wide chlorine were recognized in the
are now occurring after intravitreal range of available antiseptics, with 1700s and soon it was used to prevent
injections of antivascular endothelial varied efficacies against multitudes infection in wounds and as a gargle for
growth factor (VEGF) medications for of microbes. However, just as with infected sore throats. After it helped
choroidal neovascularization related antibiotics, resistance can be a concern, curb the cholera epidemic of the 19th
to age-related macular degeneration,8-11 and it’s important to preserve the ability century, chlorine was used to create
diabetic cystoid macular edema,12,13 of antiseptics to control and prevent an entire class of N-chloro compounds.
and retinal vein occlusion14. Infact, ocular infections. Iodine and hydrogen peroxide became
current protocols for the treatment prevalent antiseptics in the 19th
of neovascular age-related macular History and Background century, and both are still used today.
degeneration dictate monthly or near- Discoveries of antiseptics and The 20th century saw the development
monthly injections of anti-VEGF15. preservatives were initially linked to of quaternary ammonium compounds
The risk of endophthalmitis reported humanity’s ambition for expansion and such as chlorhexidine, which is one of
after intravitreal injections isbetween conquest. Early travel was inhibited the most recent advances in antiseptic
0.022% and 0.16%16,17. by innocuous wounds developing into research.
Surgeons therefore use antiseptics as a lethal infections as well as food and Iodine has been used for 150 years. It
part of routine preoperative procedures water contamination and spoilage. is still a potent agent against bacteria,
to sterilize the ocular surface and In about 450 BC, the Persians realized viruses, fungi amoeba and other
surrounding area. Antiseptics are also that copper and silver-lined containers pathogens.
maintained water’s freshness. Boiling

20 DOS Times - Volume 25, Number 5, March-April 2020 www.dosonline.org/dos-times

Beyond Ophthalmology

Antiseptics are used for surgical common practice around this time, used it for the treatment of bronchocele
sterilization, treatment of infection, although heat sterilization was not and tuberculous skin lesions, but
prophylaxis and medication widespread until after the discoveries of stability problems, skin staining,
preservation. Endophthalmitis Louis Pasteur in the 18th century. stinging in open wounds, allergies and
arising from cataract surgery is a rare mucosal toxicity hindered its use.
Records from the 4th century indicate
but serious complication thought the use of mercury by Arab physicians Today, modern medical
to derive largely from microflora in as an antiseptic-until its toxic effects
the ocular tear film, lids and adnexa were realized. Throughout the formulations are compounded with
centuries, people discovered the polyvinylpyrrolidone. Povidone-iodine
gaining entry to the anterior chamber antiseptic properties of silver, copper (PVI) is used in every medical arena,
during surgery. Similarly, refractive and zinc. The bleaching powers of
surgery poses the risk of keratitis, chlorine were recognized in the whenever the skin is to be ruptured.
1700s and soon it was used to prevent It was approved as a dermatological
with microflora entering the cornea. infection in wounds and as a gargle for solution in the 1950s, and then as an
Surgeons therefore use antiseptics as a infected sore throats. After it helped
part of routine preoperative procedures curb the cholera epidemic of the 19th ophthalmic solution in 1986. It’s used
century, chlorine was used to create prophylactically to kill and hinder the
to sterilize the ocular surface and an entire class of N-chloro compounds. growth of bacteria prior to surgery, both
surrounding area. Antiseptics are also Iodine and hydrogen peroxide became
used routinely in neonatal conjunctiva. prevalent antiseptics in the 19th on the skin and in the eye for ocular
century, and both are still used today. surgical procedures. In its 150 years
Doctors prophylactically instill drops The 20th century saw the development of use, PVI has demonstrated potent
of silver nitrate, erythromycin or of quaternary ammonium compounds
tetracycline bilaterally into neonates to such as chlorhexidine, which is one of bactericidal, fungicidal, virucidal,
the most recent advances in antiseptic amoebicidal and sporicidal properties.
prevent disease, per recommendations research.
of the Centersfor Disease Control
and Prevention. Antiseptics and The Galaxy of Antiseptics Povidone– iodine (PVI) is a disinfectant
Molecular iodine has inherent antiseptic and antiseptic agent used for
preservatives fall under the umbrella properties due to its electronegativity. preoperative preparation of the skin
of biocides, which also includes In solvent-based systems, diatomic
disinfectants (agents used on nonliving neutral (i.e., free) iodine has the ability and mucous membranes, as well as for
to oxidize thiol moieties (-SH) with the the treatment of contaminated wounds.
surfaces). Antiseptics, which are rapid formation of disulfides (R-SS-R). Because of its broad spectrum of
bactericidal, are used to prevent sepsis Additionally, free iodine can undergo
substitution for hydrogen on activated microbicidal activity, PVI is used widely
through decreasing the bacterial load, aromatic systems (including many in ophthalmology. Preparation of the
naturally occurring amino acids) and
while bacteriostatic preservatives mono- or di-iodination with certain eyelids, eyelashes, and conjunctiva prior
are used to prevent bacterial growth. olefins that are present in all unsaturated
Some biocides, such as povidone- fatty acids. As the uncharged free iodine to intraocular surgery decreases the risk
can easily pass through the cell walls of endophthalmitis. Disinfectants are
iodine, have crossover capabilities of microorganisms, it’s thought that classified into three levels depending
all of these reactions contribute to the
and have wide applications and high germicidal efficacy of iodine in living on the spectrum of microbial activity.
degrees of efficacy. There is a wide microorganisms. Though molecular
range of available antiseptics, with iodine is an effective antiseptic in High-level disinfectants are used for
aqueous or alcoholic solvents, its use sterilization of medical instruments and
varied efficacies against multitudes was originally limited by poor solubility, their use is limited to this indication. PVI
dramatic chemical instability and
of microbes. However, just as with severe irritation of mucous membranes. is an intermediate-level disinfectant,
antibiotics, resistance can be a concern, In the 1800s, the French doctor J.G.A.
and it’s important to preserve the ability Lugol developed a solution of elemental which can be used for skin disinfection.
iodine with iodine potassium salts and It is effective against multidrug resistant
of antiseptics to control and prevent bacteria, Pseudomonas aeruginosa,

ocular infections. Mycobacterium tuberculosis, fungi,

Background and Development and hepatitis virus, but not spores.
Discoveries of antiseptics and PVI is additionallyactive in biofilms
preservatives were initially linked to and againstAcanthamoeba. PVI is
humanity’s ambition for expansion and composed of diatomic iodine and
conquest. Early travel was inhibited polyvinylpyrrolidone (povidone).
by innocuous wounds developing into Povidone is a watersoluble polymer that
lethal infections as well as food and serves as a carrier for iodine. It is a dry
water contamination and spoilage. powder, allowing easy transportation
In about 450 BC, the Persians realized and use in a remote environment. The
that copper and silver-lined containers solubility in water depends on the
maintained water’s freshness. Boiling chain length of PVI between 5% (type
water before drinking also became 90/04, average molecular weight near

www.dosonline.org/dos-times DOS Times - Volume 25, Number 5, March-April 2020 21

Beyond Ophthalmology

1000000) and more than 20% (type Figure 1: Presurgical periocular application and scrubbing of lids with Povidone-iodine.
17/12, average molecular weight near
10 000)14. A 10% PVI solution contains (1%) was successful in reducing the 0.2 % povidone-iodine is then applied to
1% available iodine. Iodine oxidizes infectivity of the virus (both SARS-CoV the conjunctival sac for 5 minutes. The
water to release ions that directly act and MARS-CoV, 1-min time contact conjunctival fornix and cornea are then
onbacterial or viral membrane proteins period for SARS-CoV and 15-second prepared with 10 concentric individual
to exhibit microbicidal effect15. As iodine contact time for MERS-CoV, were sterile swabs of 0.2% povidone-iodine.
also acts on membrane proteins of associated with significant loss of viral After the patient is transferred to
normal human cells, a balance between infectivity)23. Occurrence of resistance a surgical suite, the eyelids are re-
an effective and nontoxic concentration is not an issue with povidone iodine. scrubbed with 5% povidone-iodine, and
needs to be achieved. Furthermore, So, here comes a theoretically potential a drop of sterile hyaluronate solution
appropriate exposure time is essential16. role of using povidone iodine 1% locally is placed in the eye before draping.
PVI can be suspended in hydrogels such (eye drop) in case of accidental ocular Intraocular surgery (cataract surgery
as polyvinyl alcohol, carboxymethyl exposure or in case of 2019-nCoV- and lens extraction) requires copious
cellulose, gelatin, and cross-linked associated conjunctivitis. However, volumes of sterile saline, necessitating
polyacrylamide. The release rate of toxicity profile of povidone iodine is to waterproof adhesive draping that
iodine is dependent on the chemical be to be considered and we need more prevents the wicking of epidermal
structure and the concentration of the clinical data for further validation. bacteria back towards the eye24,25,26.
hydrogel– iodine matrix17.
After penetrating the membranes of High concentrations of, and increased Povidone-iodine has many ideal
microorganisms, PVI reacts with key contact time with, povidone-iodine characteristics, including
proteins and nucleotides through the can also oxidize and damage both
mechanisms described above, inducing corneal and conjunctival proteins. • Low cost
cell lysis, according to information Povidone-iodine is therefore routinely • Rapid and broad-spectrum anti-
provided by International Specialty diluted to between 5 and 10% for eyelid
Products, an iodine maker. It’s more applications and to 0.2% for corneal microbial
effective against non lipid-enveloped and conjunctival tissue. A typical pre- • Low toxicity
viruses, likely due to affinity for the surgical ocular application begins with • High water solubility
surface proteins on the lipid membrane. 10 concentric gauze-based scrubs of • Absence of microbial resistance
One interesting observation is that more the eyelids and surrounding skin with • Ease of application and storage
dilute formulations of PVI demonstrate 5% povidone-iodine (Figure 1). The In addition to PVI, a battery of other
greater and more rapid killing efficacy scrubbing increases contact time of antiseptics are in use. Chlorhexidine
than more concentrated ones, while the aqueous iodine with the skin and glucate (CHX), for example, has been
also being less irritating to mucosal produces shearing forces that destroy used for more than 30 years against
surfaces. To this end, the ophthalmic biofilms (microbial aggregates). bacterial skin infections, open wounds
solution ranges from 1.25% to 5% while and gingivitis. Commercially available
the dermatological solution ranges The conjunctival sac and cornea are chlorhexidine-based products include
from 5% to 10%. then flushed with 150 ml of sterile Peridex Oral Rinse and Hibistat
Now, coming to the efficacy of povidone saline to further dislodge bacteria and Towlettes. Through extemporaneous
iodine treatment in SARS-CoV, other organic material. A further 5 ml of
treatment with povidone iodine for 2
min reduces viral infectivity to below
detectable level and the efficiency of
povidone iodine was similar to 70%
ethanol in terms of reducing viral
infectivity18. There are reports citing
efficacy of povidone iodine gurgle/
mouth wash against SARSCoV and
MERS-CoV19,20, and on the basis of these
findings, povidone iodine mouth wash/
gurgle is being recommended in cases of
SARS-CoV-2 also21,22 by various authors.
In in vitro studies, povidone iodine

22 DOS Times - Volume 25, Number 5, March-April 2020 www.dosonline.org/dos-times

Beyond Ophthalmology

compounding, chlorhexidine has also Figure 2: Natural production of Hypochlorous acid.
been investigated as a 0.02% drop
for ocular and mucosal infections. therapy as blepharitis is chronic and This compound is an oxidant that kills
Chlorhexidine, although pH-dependent relief of symptoms may be temporary. bacteria through protein and lipid
and therefore of varying efficacy, is a A new therapeutic approach for the peroxidation and/or halogenation.
broad-spectrum antiseptic, disinfectant treatment of blepharitis is the use of HOCl has a broad spectrum of activity
and preservative. Bacterial uptake stabilized hypochlorous acid (HOCl)31. and exhibits rapid kill kinetics.
of chlorhexidine has been shown The compound (0.01%) is the key
to be very rapid, with maximum In nature HOCI is formed by preservative ingredient in an ocular
bioavailability reached in less than polymorphonuclear neutrophils to hygiene product that is designed to
20 seconds. Chlorhexidine damages killmicroorganisms32, and commercial clean the area around the lids and
the cell membrane and then causes formulations have been shown to be lashes.
intracellular elements to leak useful in treatment of non-healing HOCl has different mechanisms from
through the resulting semi-permeable wounds that are also associated with antibiotics for killing bacteria. The
membrane. It also has a biphasic chronic infection by staphylococci and compound acts as an oxidant and its
lethal effect: Once concentrations of other microbes. Beyond blepharitis, it is bacteriocidal effect is the result of
chlorhexidine become high in the target possible that hypochlorous acid could lipid peroxidation or halogenation. If a
cell, the cytoplasm begins to coagulate, be used for prophylaxis prior to ocular reduction in the bacterial load occurs
reducing leakage and then inhibiting surgeries and as an alternative or in without the loss of commensal bacteria
enzyme activity27. addition to other anti-infective agents species33, treatment with HOCl hygiene
such as povidone-iodine. solution could be beneficial.
Efficacy of chlorhexidine may vary. Eyelid hygiene cannot replace general
In a small study (n=5) of patients Hypochlorous acid (HOCl) is a natural preoperative procedures focused on
infected with Acanthamoeba keratitis antibacterial agent. Pure HOCl is preventing contamination, such as
(AK), CHX was found to be effective produced naturally as an element of the use of PVI solutions for eyelids
at a concentration of only 0.006%. the human immune response (Figure and conjunctiva or antibiotics.
Symptoms decreased within a week, 2). During the “oxidative burst”, small, Nevertheless, eyelid hygiene can be
ulcers were healed in a mean of 19 highly reactive molecules, such as used as a complementary prophylactic
days, and visual acuity improved by HOCl, are generated as white blood
80 percent in two to three weeks. cells respond to pathogens in the body.
Acanthamoeba keratitis did recur in
one patient but was eradicated with
persistent dosing of CHX28.

Stabilized Hypochlorous Acid
(HOCL)
Blepharitis, or inflammation of the
eyelids, is a chronic ocular surface
disease. Patients present with
significant discomfort and symptoms
that include redness, itching, burning,
foreign body sensations, and blurred
vision29. Though bacteria may or may
not initiate blepharitis, the oily and
inflamed eyelid margins of blepharitis
patients are frequently colonized by
bacteria, predominantly by Gram-
positive bacteria including species of the
Staphylococcus, Propronibacterium,
and Corynebacterium genera30.

Current treatment routines include
cleaning the eyelids, the use of warm
compresses, and often the use of topical
antibiotics. However, many individuals
with blepharitis require long-term

www.dosonline.org/dos-times DOS Times - Volume 25, Number 5, March-April 2020 23

Beyond Ophthalmology

approach to prevent endophthalmitis. ocular surgery. Acta Ophthalmol [Internet] 24. Povidone Iodine Antiseptic Agent.
The use of HOCL and cleansing 2017; 95:e253–e254. International Specialty Products, 2004:
eyelid wipes may help in the case of 1-32.
undiagnosed blepharitis before cataract 13. Gottardi W. Iodine and iodine compounds.
surgery or other kinds of ocular surgery, In: Block SS, ed. Disinfection, Sterilization, 25. Arup Chakrabarti et al. Povidone-Iodine
as they could also reduce the risk of and Preservation. Philadelphia, London: in ophthalmology. Kerala Journal of
postoperative endophthalmitis. Lea & Febinger; 1991. pp. 152–166. Ophthalmology.2007; 29(3): 282-286.

References 14. Shelanski HA, Shelanski MV. PVP-iodine: 26. Kairuz T, Chhim S, Hasan F, Kumar K,
history, toxicity and therapeutic uses. J Int Lal A, Patel R, Singh R, Dogra M, Garg
1. Ciulla TA, Starr MB, Masket S. Bacterial Coll Surg 1956; 25:727–734. S. Extemporaneous compounding in
endophthalmitis prophylaxis for cataract a sample of New Zealand hospitals:
surgery: An evidence-based update. 15. Shimada H, Nakashizuka H, Grzybowski A. A retrospective survey. NZ Med J
Ophthalmology 2002;109:13-24. Prevention and treatment of postoperative 2007;120:1250:1-9.
endophthalmitis using povidone-iodine.
2. Isenberg SJ, Apt L, Wood M. A controlled Curr Pharm Des 2017; 23:574–585. 27. Kosrirukvongs P, Wanachiwanawin
trial of povidone iodine as prophylaxis D, Visvesvara GS. Treatment of
against ophthalmia neonatorum. N Engl J 16. Mishra A, Chaudhary N. Study of povidone
Med 1995;332:9:562-566. iodine loaded hydrogels as wound dressing acanthamoeba keratitis with
material. Trends Biomater Artif Organs
3. Amanda Howe, Joseph Capriotti, 2010; 23:122–128. chlorhexidine. Ophthalmology
MD, and Aron Shapiro . Get to Know 1999;106:4:799-802.
Your Antiseptic Options . Review of 17. Kariwa H, Fujii N, Takashima I (2006)
Ophthalmology April 16,2008 . Inactivation of SARS Coronavirus by 28. Lemp MA, Nichols KK. Blepharitis in
means of povidone-iodine, physical the United States 2009: a survey-based
4. Hugo WB. A brief history of heat and conditions and chemical reagents. perspective on prevalence and treatment.
chemical preservation and disinfection. J Dermatology (Basel, Switzerland) Ocul Surf. 2009; 7:S1–S14. [PubMed:
Appl Bacteriol 1991;71:1:9-18. 212(Suppl 1):119–123. 19383269]

5. Hugo WB. A brief history of heat and 18. Eggers M, Koburger-Janssen T, Eickmann 29. Lindsley K, Matsumura S, Hatef E, Akpek
chemical preservation and disinfection. J M, Zorn J (2018) In vitro bactericidal and EK. Interventions for chronic blepharitis.
Appl Bacteriol 1991;71:1:9-18. virucidal efficacy of povidone-iodine Cochrane Database Syst Rev. 2012:
gargle/mouthwash against respiratory
6. Gottardi W. Iodine and iodine compounds. and oral tract pathogens. Infect Dis Ther 30. Stroman DW, Mintun K, Epstein AB,
In: Block SS, ed. Disinfection, Sterilization, 7(2):249–259. Brimer CM, Patel CR, Branch JD, Najafi-
and Preservation, Fifth Edition. Lippincott Tagol K. Reduction in bacterial load using
Williams & Wilkins, 2000:159-204. 19. Eggers M, Eickmann M, Zorn J (2015) hypochlorous acid hygiene solution
Rapid and effective virucidal activity of on ocular skin. Clin Ophthalmol. 2017;
7. Workowski KA, Levine WC. Sexually povidone-iodine products against Middle 11:707–714.
transmitted diseases treatment guidelines East Respiratory Syndrome Coronavirus
2002. CDC Recommendations and Reports (MERS-CoV) and Modified Vaccinia Virus 31. Hurst JK. What really happens in the
2002;51:RR06:1-80. Ankara (MVA). Infect Dis Ther 4(4):491– neutrophil phagosome? Free Radic Biol
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8. Najafi RB, Samani SM, Pishva N, Moheimani
F. Formulation and clinical evaluation of 20. Kirk-Bayley J, Combes J, Sunkaraneni S, 32. Avenova® with Neutrox® [package
povidone-iodine ophthalmic drop. Iranian Challacombe S (2020). The use of Povidone insert]. Emeryville, CA: NovaBay
J Pharm Res 2003;2:157-160. iodine nasal spray and mouthwash Pharmaceuticals, Inc.; 2014.
during the current COVID-19 pandemic
9. Barkana Y, Almer A, Segal O, Lazarovitch may reduce cross infection and protect 33. Assumpta Peral, Jose Alonso, Concepción
Z, Avni I, Zadok D. Reduction of healthcare workers. Soc Sci Res Netw. García-García,Importance of Lid Hygiene
conjunctival bacterial flora by povidone- Before Ocular Surgery: Qualitative
iodine, ofloxacin and chlorhexidine in an 21. Mady LJ, Kubik MW, Baddour K, and Quantitative Analysis of Eyelid
outpatient setting. Acta opthalmologica Snyderman CH, Rowan NR (2020) andConjunctiva Microbiota ,Eye &
Scandinavica 2005;83:3:360-363. Consideration of povidone-iodine as a
public health intervention for COVID-19: Contact Lens 2016;42: 366–370).
10. Speaker MG, Menikoff JA. Prophylaxis of utilization as “personal protective
endophthalmitis with topical povidone- equipment” for frontline providers Corresponding Author:
iodine. Ophthalmology 1991; 98:1769– exposed in high-risk head and neck and
1775. skull base oncologycare.Oral Oncol Dr. Jatinder Singh Bhalla
Published online April 16. MS, DNB, MNAMS
11. Garner JS, Favero MS. CDC guidelines for Senior Consultant & HOD (Ophthal)
the prevention and control of nosocomial 22. Kampf G, Todt D, Pfaender S, Steinmann DDU Hospital, New Delhi
infections. Guideline for handwashing E (2020) Persistence of coronaviruses on
and hospital environmental control, inanimate surfaces and their inactivation
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23. Speaker MG, Menikoff JA. Prophylaxis of
12. Grzybowski A, Brona P. Povidone-iodine endophthalmitis with topical povidone-
is still a premium antiseptic measure in iodine.Ophthalmology 1991; 98: 769-75.

24 DOS Times - Volume 25, Number 5, March-April 2020 www.dosonline.org/dos-times

What’s New

Upneeq

Anasua Ganguly Kapoor MD, DNB, FICO (UK)
Fellow All India Collegium of Ophthalmology
Consultant
Ophthalmic Plastic Surgery, Ocular Oncology & Aesthetic Services
L.V. Prasad Eye Institute, Vijaywada, India.

Upneeq (oxymetazoline hydrochloride for at least 6 weeks. Both trials reported single patient-use container to their
ophthalmic solution, 0.1%) is a novel that Upneeq showed statistically eye or to any surface, in order to
non-surgical treatment for acquired significant improvement in superior avoid eye injury or contamination
blepharoptosis approved by USFDA on visual field as well as marginal reflex of the solution.
9th July 2020. distance 1 (MRD1) compared to the Commercial availability
placebo group. Company intends to make Upneeq
Manufacturer available in market by August 2020.
Adverse Drug Reaction References
Osmotica Pharmaceuticals 1. “UPNEEDQ® Label” (PDF). accessdata.
Adverse reactions occurred in 1-5% and fda.gov. 8 July 2020.
Mechanism of action were mostly mild and self resolving 2. https://www.drugs.com/history/upneeq.
like: punctate keratitis, conjunctival html.
Oxymetazoline is an alpha- hyperemia, dry eye, blurred vision, 3. https://www.empr.com/home/news/
adrenoceptor-agonist targeting a subset instillation site pain, eye irritation and uneeq-approved-blepharoptosis-
of adrenoreceptors in Muller’s muscle headache. oxymetazoline-hydrochloride-
to elevate the eyelid. ophthalmic-solution-osmotica.
Contraindications: None 4. h t t p s : / / w w w . h e a l i o . c o m / n e w s /
Indication for Usage ophthalmology/20200710/fda-approves-
Warning and Precautions: novel-therapy-for blepharoptosis.
Upneeq is indicated in acquired
blepharoptosis in adults. a) In Cardiovascular disease- To be Corresponding Author:
used with caution in patients with
Dosage Form and Strength severe or unstable cardiovascular Dr. Anasua Ganguly Kapoor
disease, orthostatic hypotension, MD, DNB, FICO (UK)
Ophthalmic solution, 0.1% and uncontrolled hypertension or L.V. Prasad Eye Institute, Vijaywada, India.
oxymetazoline as salt (equivalent hypotension.

to 0.09% oxymetazoline as base) b) In vascular insufficiency- To be
aseptically prepared, sterile, non- used with caution in patients with
preserved, clear, colorless to slightly cerebral or coronary insufficiency,
yellow or Sjogren’s syndrome.

Dosage and Administration: Instill one c) In angle closure glaucoma- Upneeq
drop into one or both ptotic eye(s) once may precipitate angle closure in
daily. patients with untreated narrow
angle glaucoma.
Efficacy
Patient to seek medical help
Upneeq was evaluated for the treatment immediately in case their
of acquired blepharoptosis in two preexisting signs and symptoms
randomized, double-masked, placebo- worsen.
controlled, parallel-group clinical
efficacy trials. In both the trials once d) Risk of contamination- Patients
daily treatment was given with Upneeq should not touch the tip of the

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Subspeciality-Cornea

Corneal Allogenic Intrastromal
Ring Segments (CAIRS) for Treating
Keratoconus, other Corneal
Ectasias and Synthetic ICRS
Related Melts

Sanjana Vatsa MBBS MS, FPRS, FCRS, Soosan Jacob MBBS, MS, FRCS, DNB
Director and Chief, Dr. Agarwal’s Refractive and Cornea Foundation, Senior Consultant, Cataract and Glaucoma Services, Dr. Agarwal’s
Group of Eye Hospitals, Chennai, Tamil Nadu, India

Dr. Jacob has a patent pending for special trephines, devices and processes used to create these segments as well as for the CAIRS segments
and various types of shaped corneal segments

Keratoconus is a condition characterised much topographic improvement and thickness in the zone of implantation,
by progressive thinning and steepening cannot be performed in very thin and thus limiting it’s usage in more advanced
of the central or paracentral cornea steep corneas. Though DALK provides cases of keratoconus. Presence of a hard
associated with the induction of good visual and refractive outcomes synthetic material within the cornea
irregular astigmatism resulting in loss in severe keratoconic eyes, it comes hinders the passage of oxygen and
of uncorrected visual acuity (UCVA) with disadvantages such as usage of nutrient. Other than the complications
and best corrected visual acuity (BCVA). topical steroids and other medications mentioned previously, these synthetic
This disease considered a bane by both for a longer time post operatively along segments can also migrate and override,
Ophthalmologists and patients has with consequent medication induced cause neovascularisation, infections,
seen a progress in both diagnosis and complications, delayed visual recovery, delayed acute hydrops, inflammation,
treatment in recent times. graft and suture related induction peri-channel deposits, focal edema,
of irregular astigmatism, chances of corneal haze etc.
The three key and most commonly rejection, suture related complications
used surgical options available for the etc. CAIRS
management of keratoconus include: One of the authors (SJ) thought
1. Corneal collagen cross linking ICRS are small curvilinear synthetic of combining the advantages on
segments, implanted at a depth of 70- biomechanics and topography of ICRS
(CXL) 80% of corneal stroma which acts as while overcoming the disadvantages
2. Intracorneal ring segments (ICRS) spacer elements between the collagen associated with the synthetic material
3. Deep anterior lamellar keratoplasty fibres and flattens the central cornea by implanting corneal stroma shaped
by its arc shortening effect and thus to the form of ring segments into
(DALK) regularises the shape of the keratoconic femtosecond laser dissected channels
corneas. With a complication rate of up within the patient’s stroma.
Limitations of Current to 30%, there is understandably some
Treatment Modalities hesitancy to implant these devices Corneal allogenic intrastromal ring
Though these are proven to be despite the good visual outcomes. segments (CAIRS) refers to the use of
advantageous, they do come with Major complications include migration, allogenic tissue as intracorneal ring
certain limitations which make them corneal necrosis, melt, extrusion, segments. The use of human stromal
less suitable in a multitude of cases. intrusion, exposed segment, infectious tissue eliminates the disadvantages
CXL is safe and effective in arresting keratitis etc. In addition, they cannot be which are associated with synthetic
the progression and improving the implanted in very thin corneas < 450 µm ICRS while having the advantage of
biomechanical strength of keratoconic
corneas. However, it may not contribute

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Subspeciality-Cornea

improving topography and vision. or in case of thinner corneas, with We chose 50% depth of implantation.
CACXL (contact lens-assisted corneal A deeper implantation would increase
Mechanism of Action cross-linking). After the placement the posterior curvature and decrease
CAIRS acts as a spacer graft and of segments, epithelium is removed myopic refractive error, but would
centralizes the cone, thus regularising carefully, going perpendicular in the have limited effect on regularisation of
the corneal topography which in turn areas over the segments, taking care not topography. Superficial implantation
improves the uncorrected and best to move the segments. It is important flattens and regularises the corneal
corrected visual acuity and quality to remember that immediately after surface but the effect on posterior
of vision. It also helps in arresting implantation, some mobility of the corneal curvature would be lost.
the progression of keratoconus by segments is normal but very soon, Thus we chose implantation at mid-
redistributing the corneal stress forces. the segments adhere well to the host depth in order to obtain beneficial
stroma because of capillary action effects of increasing the posterior
Procedure (very similar to a LASIK flap being corneal curvature, flattening the
Human donor corneal tissue is de- very mobile immediately after surgery anterior corneal curvature as well
epithelialised and de-endothelialised. but adhering well after some time). as regularizing corneal topography,
A double bladed circular trephine Cross-linking is then proceeded with thereby significantly reducing the
with two concentric blades is used to according to the protocol selected. myopic power as well as improving the
punch out a circular segment from Riboflavin solution is applied for half overall quality of vision. In addition, we
the donor cornea. This is then cut into an hour on the corneal surface followed were also able to decrease astigmatic
two halves using a blade. The segments by UV light application. A bandage error by using shorter arc lengths.
are flattened out and if required, split contact lens is applied until epithelial
longitudinally into appropriate size. healing is complete. CACXL involves 3. Implantation in Thinner and Steeper
Meanwhile, femtosecond channels for an additional step where in a non UV Cornea
the insertion of CAIRS are created on blocking soft contact lens is soaked in CAIRS is safe even in thinner
the cornea using standard technique. riboflavin for half an hour and the lens corneas with pachymetry (in zone of
Two entry incisions are preferred, is placed on the eye during UV exposure implantation) less than 450 microns.
though with experience, one may which artificially increases the Steeper corneas where we would
also suffice. The parameters that can thickness of cornea and thus ensures have previously avoided cross linking
be varied are inner diameter, outer safety in thinner corneas. In patients due to associated risk and would
diameter, depth of insertion as well as aged 30-40 years or more with no signs have performed anterior lamellar
segment thickness and arc length. The of progression or in already cross-linked keratoplasty can now be treated with
allogenic nature of the segments allows patients, CAIRS alone can be done CAIRS. The initial flattening created by
more superficial implantation than without CXL. the CAIRS segments makes the cornea
synthetic ICRS and we prefer to do this suitable for safe subsequent cross-
at 50% of the minimum pachymetry Advantages of CAIRS linking. This has helped in preventing
in the implantation zone. Two entry 1. Biocompatibility corneal transplantation and its
incisions into the channel are created The allogenic tissue containing human associated complications in many cases.
180° apart on the topographic steep axis. donor cornea used in CAIRS provides
Both incisions are then opened up using good bio compatibility and gets 4. Visual and Refractive Improvement
a symmetric glide. The prepared CAIRS integrated well into the host cornea. Our study on outcomes of CAIRS
segments are inserted into the tunnels (published in 2018, JRS) included
with a push-in/pull-through technique 2. Superficial Insertion 24 eyes from 20 patients with
using a curved and twisted Y-rod and a It can be implanted superficially at a different stages of keratoconus. The
reverse Sinskey hook. Any extra length depth of 50 % as against ICRS which postoperative follow up period ranged
of the segment is trimmed and the are implanted deeper at a depth of 70- from 6-18 months. On comparing
segments are positioned well within the 80 %. CAIRS thus provide better visual preoperative and postoperative
channel ensuring at least a gap of 1mm and topographical outcomes. CAIRS parameters, it was found that there was
on either side of the segment to the may also be placed more superficial a significant improvement in UCVA,
incision. This gap can be more in case or more deep, depending on surgeon’s BCVA and spherical equivalent. There
of shorter arc segments. These segments preference without increased risks in was a mean improvement of 2.79 ±
can also be cut to different thicknesses contrast to synthetic segments which 2.65 lines (range: 0 to 8 lines) in UDVA
and arc lengths, with even up to 360° must be implanted deeper at a depth of comprising 12 eyes (50%) with three
implantation being possible. 70-80 % and have at least 400 microns or more lines, 5 eyes (20.83%) with one
stroma above the synthetic material. and two lines, and 7 eyes (29.16%) with
CAIRS can also be combined with CXL no improvement. CDVA improved by a

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Subspeciality-Cornea

such as Intacs (Addition Technology)
and Keraring (Mediphacos). This
involves removing the synthetic ICRS
causing the melt and implanting an
appropriately sized CAIRS segment
into the same channel. The segment is
held in place in the initial postoperative
period with anchoring sutures at either
end. Bridging sutures passing over the
segment helps further in holding the
segments in place in the initial post-
operative period.

Figure 1: CAIRS (Corneal Allogenic Intrastromal Ring Segment): Post CAIRS with CACXL Conclusion
in a 20 year old girl with keratoconus. Notice the large area of flattening achieved. Mild
steepening in the pre-operative flat axis leads to an overall decrease in cylinder and overall In our experience of more than 4 years,
topographic regularization. Sphere and cylinder have decreased significantly. CAIRS has proven its safety, efficacy,
biocompatibility and reversibility. It is
mean of 1.29 ± 1.33 lines (range: 0 to 5 Anterior segment OCT (ASOCT) serves simple to perform and tissues are easily
lines) with an improvement of three of as a useful tool to measure the corneal available. It is also more economical
more lines in 4 eyes (16.66%), between thickness pre and postoperatively. Our than synthetic segments while giving
one and two lines in 11 eyes (45.83%), study showed no significant difference excellent results and less complications.
and no improvement in 9 eyes (37.5%). between the two. It also helps in Thus CAIRS is an excellent option for
No eye showed loss of UDVA or CDVA. assessing the depth of implantation the treatment of keratoconus, other
Also, all treated eyes remained stable of the segments. ASOCT showed well corneal ectasias as well as for post
with no signs of progression. The placed segments at mid stromal depth INTACS melts.
improvement in the overall quality of with a healthy stromal tissue without
vision was attributed to the flattening signs of incompatibility such as References
of cornea, regularisation of the cone and necrosis, edema or inflammation.
decrease in the higher order aberrations. 1. Jacob S, Patel SR, Agarwal A, Ramalingam
6. Lower Chances of Rejection A, Saijimol AI, Raj JM. Corneal Allogenic
5. Topographic Improvement Rejection, though theoretically can Intrastromal Ring Segments (CAIRS)
The comparison of preoperative and occur, is rare in our current experience Combined With Corneal Cross-linking
postoperative topographic maps shows with over 150 eyes. This tolerance may for Keratoconus. J Refract Surg. 2018
a significant decrease in the topographic be attributed to lower volume of tissue May 1;34(5):296-303.
astigmatism, maximum keratometry, transplanted, intrastromal placement,
steepest keratometry, anterior and no endothelial or epithelial tissue being 2. Jacob S. CAIRS: a new technique for
posterior best fit spheres, and mean transferred, placement far from the keratoconus and corneal ecstasias. www.
power in the 3- and 5-mm zones. limbus and limbal blood vessels and youtube.com/watch?v=qf-9ycsqpq8.
Although CAIRS are soft, non-rigid lack of sutures extending to the limbus Published May 9, 2017. Last accessed
and pliable in nature, they produce a (unlike corneal transplants). We use 4/4/20.
significant flattening of the keratoconic topical steroids post-operatively for a
corneas. This can be explained by the short period of 6 weeks only. Even in 3. Jacob S. CAIRS (Corneal Allogeneic
Barraquer thickness law, which states the worst case scenario of a rejection, Intrastromal Ring Segments) for
that the flattening achieved is directly there would be no drop in vision and keratoconus, ectasias & irregular
proportional to the thickness of the the segments would still continue to corneas. www.youtube.com/
segment and inversely proportional provide improvement in topography watch?v=skxlwgp8cxa. Published Feb.
to its diameter. Thus thicker segments and vision since they are implanted 24, 2019. Last accessed 4/4/20.
placed within a smaller optic zone in in the mid-periphery well outside the
the donor cornea produce significant visual axis. 4. Larkin H. CAIRS for Keratoconus.
topographic regularisation. This also https://www.eurotimes.org/cairs-for-
helps in improving the contact lens Special Indications of CAIRS keratoconus. Published on April 1, 2019.
tolerance in irregular corneas. We have also used CAIRS to treat corneal
melts related to synthetic segments 5. Caceres V. CAIRS may eliminate
complications from synthetic ring
segments. Ophthalmology Times;
Published March l8, 2019. https://www.
ophthalmologytimes.com/article/cairs-
may-eliminate-complications-synthetic-
ring-segments

6. Jacob S. Allogenic Ring Segments for
Keratoconus. Published Nov 30, 2017.

28 DOS Times - Volume 25, Number 5, March-April 2020 www.dosonline.org/dos-times

Subspeciality-Cornea

https://www.aao.org/1-minute-video/ cairs-for-keratoconus-and-pearl-for- Corresponding Author:
allogenic-ring-segments-keratoconus presbyopia/
Dr. Soosan Jacob MBBS, MS, FRCS, DNB
7. Allogenic Intrastromal Ring Segments 10. Jacob S, Patel S. Intrastromal corneal Director and Chief,
for Corneal Ectasia. Interview with Ring Segments. Chapter 15, pg 282-97; Agarwal’s Refractive and Cornea Foundation,
Rahul T Pandit from AAO 2017; https:// Gems of Ophthalmology: Cornea & Senior Consultant, Cataract and Glaucoma
www.aao.org/interview/allogenic- Sclera (Eds HV Nema, Nitin Nema) Services, Dr. Agarwal’s Group of Eye Hospitals,
intrastromal-ring-segments-corneal- Chennai, Tamil Nadu, India
ectas 11. Hillman L. Is it the age of allogenics? Eye
World, Dec 2017: https://www.eyeworld.
8. CAIRS interview with Jonathan Kahn org/it-age-allogenics-0
(EyeWorld) at ASCRS 2019 Annual
Meeting. https://www.facebook.com/ 12. Jacob S. Corneal Allogenic Intrastromal
watch/?v=2618806451491385 Ring Segments: An Alternative to DALK
in Certain Situations. Mastering DALK:
9. Jacob S. CAIRS for Keratoconus and Chapter 13; A Video Textbook on Deep
PEARL for Presbyopia - New treatments Anterior Lamellar Keratoplasty (Ed.
using allogenic donor tissue are on the Soosan Jacob)
horizon. CRST, Cover Focus- June 2019;
https://crstoday.com/articles/2019-june/

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Subspeciality-Cornea

Ophthalmia Neonatorum

Ritika Mukhija MD, Deeksha Rani MBBS, Ishan Mahesh Pandya MD
Department of Ophthalmology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi,
India.

Ophthalmia neonatorum, also known herpes involving the cervix at the time and Chlamydia trachomatis which are
as neonatal conjunctivitis, refers to of delivery, contract the infection. implicated in STIs. Other causes include-
conjunctival inflammation along with Haemophilus species, Streptococcus
discharge during the first month of Lack of local secretory IgA (unless pneumoniae, Staphylococcus aureus,
life. This condition can be caused by provided by adequate breast feeding), Streptococcus viridans, Pseudomonas
bacterial, viral, and chemical agents. abnormally low tear secretion in aeruginosa, Escherichia coli and
Widespread effective prophylaxis has most pre-term and about 20% of full- Klebsiella pneumonia.
contracted its occurrence to very low term infants, absence of lymphoid Viral: Herpes simplex virus (more
levels in industrialized countries, but tissue in conjunctiva, and decreased commonly HSV II) and Adenovirus
ophthalmia neonatorum remains a concentration of tear lysozymes in are also important causes of neonatal
significant cause of ocular infection, premature infants are the inherent conjunctivitis
blindness, and even death in medically factors that predispose the neonates Fungal: Though rare, Candida can also
underserved areas around the world. to the risk of developing ophthalmia be an important cause of neonatal
The prevalence ranges from 0.1% neonatorum. conjunctivitis.
in highly developed countries with The age of the baby provides important
effective prenatal and perinatal care to After birth, infection can be contracted clue towards the etiology of disease.
10% in areas such as East Africa. from the care-giver (cold-sores, Chemical conjunctivitis usually
nasopharyngeal bacteria, etc) or even presents in first 24 hours of life. Bacterial
In India, the incidence of neonatal nosocomial infections from prolonged conjunctivitis may though occur at any
conjunctivitis varies from 1% to duration of neonatal intensive care. time, is more common after 1- 2 days
24% depending upon geographical of life. After 5 days of life, Chlamydia
region. Prior to Crede’s prophylaxis, Causes trachomatis is more common followed
ophthalmia neonatorum was the Chemical conjunctivitis: Also known by Herpes keratoconjunctivitis.
main cause of neonatal blindness (60– as aseptic conjunctivitis, it is usually
75%); which often proved to be sight characterized by a mild and transient Clinical Features
threatening if not treated immediately. conjunctival injection and watering, Neonatal conjunctivitis manifests as a
which typically resolves in 24 to 48 diffuse, often hyperacute conjunctivitis
Risk Factors hours. This is caused by instillation with a papillary reaction, as a follicular
Major important risk factor is of silver nitrate into the conjunctival response is not seen prior to 6 to 8
prolonged exposure to the vaginal fornix, which was recommended by weeks of life due to immaturity of
flora, which often occurs in cases of Crede in 1881 as a prophylactic measure lymphoid system. The severity of the
premature rupture of membranes for gonococcal neonatal conjunctivitis. inflammatory response depends mainly
(PROM), prolonged delivery time, and Though this prophylaxis played a major on the inciting agent.
instrumentation during delivery. The role in reducing ocular morbidity from Gonococcal conjunctivitis: Symptoms
later may also lead to ocular trauma, neonatal conjunctivitis, it has been classically appear 2 to 5 days after
thus facilitating the invasion by largely replaced by topical antibiotics birth and is often bilateral. While an
infectious organisms. now in view of the adverse effects. earlier onset is usually associated with
premature rupture of membranes, a later
Sexually transmitted infections (STIs) in Microbial conjunctivitis: Also known as onset suggests postnatal exposure to the
the mother also play an important role septic conjunctivitis, can be bacterial, organism. An initial serosanguineous
in the etiology. 60% of infants exposed viral or fungal.
to C. trachomatis, 40% of neonates
exposed to N. gonorrhoeae and 40-60% Bacterial: The most implicated
of those exposed to primary genital organisms are Neisseria gonorrhoeae

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Subspeciality-Cornea

discharge progresses rapidly, usually perinatal risk factors, onset of HSV keratitis may also be taken.
over 24 hours to a thick and purulent symptoms and age of the baby should • Conjunctival scraping for
discharge, associated with markedly be meticulously taken as it provides
edematous eyelids and prominent important diagnostic clues. polymerase chain reaction assay
chemosis. Gonococci with their ability (PCR) is accepted as a useful test to
to penetrate intact epithelial cells and Examination detect chlamydia and HSV.
replicate rapidly, may lead to corneal • In cases of HSV, dermal or mucosal
ulceration and perforation in absence • Lids and adnexa: To look for vesicular lesions, if present, should
of prompt treatment. Gonococcal any evidence of dacrocystitis, be scraped for cytologic evaluation
infection can also give rise to systemic blepharitis, preseptal cellulitis etc with Papanicolaou stain, viral
complications like stomatitis, arthritis, culture, or immunologic testing
rhinitis, septicemia and meningitis. • Conjunctiva: Severity of • Apart from these, newer diagnostic
inflammation, type of discharge techniques like transcription-
Chlamydial conjunctivitis: With mediated amplification (TMA),
incubation period of 5-14 days, • Cornea: Corneal haze may be seen enzyme-linked immunosorbent
the onset is later than gonococcal in gonococcal keratitis. Infectious assay (ELISA) and direct florescent
conjunctivitis. The genital serovar keratitis should also be rule out. antibody (DFA) studies are useful
types D-K of Chlamydia trachomatis for detecting Chlamydia and HSV.
are responsible for causing neonatal Investigations • Cervical cultures from the mother
conjunctivitis. 30% of the effected • Conjunctival scraping for Gram may also be obtained if indicated.
neonates develop watery conjunctivitis Differential Diagnosis
which later becomes more copious stain should be done in all cases of The differential diagnosis of neonatal
and purulent. Most of the cases are neonatal conjunctivitis. Following conjunctivitis includes congenital
mild and self-limited, but occasionally findings are expected: nasolacrimal duct obstruction and
severe involvement with eyelid dacrocysitis, congenital glaucoma,
swelling, chemosis, pseudo-membrane, o Chemical conjunctivitis preseptal/orbital cellulitis and
peripheral pannus and corneal - Neutrophils, occasional infectious keratitis. They have been
involvement has been noted. Untreated, lymphocytes summarized in (Table 1). An overview
10-20% of the cases develop infantile of important infectious causes of
pneumonia, which is a major cause of o Bacterial conjunctivitis - Bacteria, Ophthalmia Neonatorum in given in
morbidity and mortality. Chlamydia neutrophils (Table 2).
may also colonize nasopharynx, rectum
and vagina. o Gonococcal conjunctivitis - Management
Neutrophils, Gram-negative Approach considerations: Preliminary
Herpes simplex keratoconjunctivitis: intracellular diplococci treatment should be started on the basis
In 80% of the neonates, it presents of clinical picture and the findings on
as generalized herpes infection with o Chlamydial conjunctivitis - Gram, Giemsa, and Papanicolaou stains.
typical herpetic lesions of the skin, Neutrophils, lymphocytes, The mother should be examined for
eye or mouth. Conjunctivitis develops plasma cells STIs and treated, if required, along with
within 6 to 14 days of birth and may be her sexual partner(s).
unilateral or bilateral and presents with o Herpetic conjunctivitis -
eyelid edema and a serous discharge. Lymphocytes, plasma cells, Neonates with conjunctivitis are at risk
Dendritic or geographical corneal ulcers multinucleate giant cells for developing secondary infections,
can also be seen. Disseminated disease such as pneumonia, meningitis,
may occur rarely and is associated with • Giemsa stain cases of Chlamydial and septicemia, which may be life-
a high mortality rate of 50%. conjunctivitis shows basophilic threatening. A thorough systemic
intracytoplasmic inclusions in evaluation and review by pediatrician
Fungal: Candida is an infrequent cause epithelial cells. should never be missed. In cases of
of neonatal conjunctivitis, with time chemical conjunctivitis, withholding
of onset after exposure being 5 days • A Papanicolaou-stained smear, the offending agent suffices, and no
or more. It may present in the eye as a which shows eosinophilic additional treatment is required.
pseudomembranous conjunctivitis or intranuclear inclusions in epithelial Symptoms usually subside in 24-48
as a white conjunctival plaque. cells, is necessary for suspected HSV hours. Tear substitutes may be used to
infection. ease any discomfort. Emphasis should
Work-up
History: History related to various • Bacterial cultures on blood and
chocolate agar are indicated in every
case of neonatal conjunctivitis and
are the standard investigations of
choice.

• In cases of suspected Chlamydial
and HSV involvement, culture of
epithelial cells is required; corneal
epithelial cells in case of associated

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Table 1: Ophthalmia Neonatorum and differential diagnoses

Condition Ophthalmia Congenital Congenital glaucoma Preseptal/ Infectious
Neonatorum nasolacrimal duct orbital keratitis
obstruction + cellulitis
dacrocystitis Fever with raised Usually no
inflammatory systemic
Associated Usually ocular With fever in case of Associated with marker May involvement
ocular/ systemic manifestation dacrocystitis megalocornea, Haab have septicemia Closely mimics
features striae and elongation of Periorbital opthalmia
globe erythema and neonatrum
edema and but with
Clinical features May have Epiphora Classical triad of pain Can have predominant
systemic predominantly with epiphora, photophobia restriction circumcilliary
manifestation mucoid or purulent and blepharospasm May of ocular congestion and
in case of herpes discharge usually have megalocornea and movement, marked corneal
and syphilis localized to puntal blue sclera and negative haziness
area Inflammation retropulsion Bilateral but can
around the medial Unilateral be unilateral
canthi
Aggressive Topical agent
Laterality Conjunctival Usually unilateral, Bilateral, rarely Intravenous specific
Management congestion rarely bilateral unilateral antibiotics chemotherapy
with epiphora with copious with
and often Topical antibiotics Urgent IOP reducing lubrication in cycloplegics
mucopurulent with Crigler drugs with glaucoma case of exposure and copious
discharge massage surgery lubricants
Cornea may Systemic antibiotics
or may not be in case of
involved dacrocystitis

Bilateral
Pathogen
targeted
chemotherapy
with copious
lubricant and
cycloplegics

be laid on maintaining ocular hygiene, extraocular infection. Cefotaxime colonization, which may be present
hourly saline irrigation should be done is also effective against resistant in 50% or more infants with
in cases of gonococcal conjunctivitis N. gonorrhoeae organisms, the neonatal chlamydial conjunctivitis.
with copious discharge. Eye patching is recommended dose for neonatal Azithromycin suspension 20 mg/
not recommended. ophthalmia being 25 mg/kg IV or kg either as a single dose or once
IM every 8 to 12 hours for 7 days. daily for 3 days.is an alternative
Specific Treatment regimen. It is also important to treat
• Gonococcal conjunctivitis: Due • Chlamydial conjunctivitis: The the caregivers with C. trachomatis
treatment of choice for neonatal infection with oral doxycycline
to emergence of widespread chlamydial conjunctivitis is oral for 7 days or with a single dose of
penicillin resistance, ceftriaxone erythromycin ethylsuccinate azithromycin.
has replaced intravenous aqueous suspension, 50 mg/kg/day in
penicillin G as the recommended three or four divided doses for • HSV conjunctivitis: All infections
treatment. A single intramuscular 14 days. Topical erythromycin caused by herpes simplex in
dose of ceftriaxone 125 mg is ointment, although clinically the neonatal period should be
highly effective against neonatal effective in conjunctivitis, plays treated with systemic acyclovir
gonococcal conjunctivitis and only an adjunctive role as it does or vidarabine. In addition, topical
also simultaneously treats not eradicate nasopharyngeal antivirals should be used in infants

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Table 2: Overview of Important Infectious Causes of Ophthalmia Neonatorum

Etiology Neisseria gonorrhoeae Herpes simplex virus Chlamydia Fungal (C. albicans)
trachomatis

Onset 2-5 days after birth 6-14 days of birth 5-14 days of birth Usually 5 days from
exposure to the source

Specific Initially serosanginous Can be unilateral or Often starts as watery Presents as a
Features discharge immediately bilateral Associated conjunctivitis, later pseudomembranous
evolving into thick with eyelid edema and becoming copious and conjunctivitis or as a
purple to discharge serous discharge purulent white conjunctival plaque
over 24 hours with Ulcers are the more Course is usually self
oedematous lids and prominent signs of limiting and resolves
chemosis corneal involvement with sequelae

Investigations Gram stain shows Conjunctival scraping Obligate intracellular Seen as hyphae or pseudo
intracellular kidney for polymerase chain gram negative organism hyphae on KOH stain
shaped gram negative reaction assay (PCR) in gram stain Other include PAS and
cocci in pairs Newer diagnostic Difficult to culture on gomori methamine silver
Culture on blood or techniques like any media Best cultured on SDA agar
chocolate agar reveals transcription-mediated Newer diagnostic
small umbonated amplification (TMA), techniques like
granular colonies Best enzyme-linked transcription-mediated
grown on Thayer Martin immunosorbent assay amplification (TMA),
media (ELISA) and direct enzyme-linked
florescent antibody immunosorbent assay
(DFA) studies are (ELISA) and direct
useful florescent antibody
(DFA) studies are useful

Treatment Single intramuscular Treatment of choice is Oral erythromycin Natamycin 5% drops
dose of ceftriaxone 125 systemic acyclovir or
mg is highly effective vidarabine ethylsuccinate hourly for 10–14 days,
Also, cefotaxime can be Other options-
given 25 mg/kg IV or IM Trifluorothymidine suspension, 50 mg/kg/ or flucytosine 1% drops
every 8 to 12 hours for 7 1% solution topically day in three or four
days every 2 hours for 7 divided doses for 14 days hourly for 10–14 days
days and no longer
than 21 days, adenine Alternatively-

arabinoside 3% Azithromycin
ointment or acyclovir suspension 20 mg/kg
5% ointment given either as a single dose or
five times daily once daily for 3 days

Prognosis Untreated cases have Mainly causes Usually leads to Prognosis poor due to
poor prognosis corneal scarring pannus formation and delayed onset and poor
May lead to and conjunctival conjunctival scarring response to treatment
corneal ulceration, membranes Blindness is usually Less fulminant than
endophthalmitis and Blindness usually to rare and late onset and bacterial
eventual blindness corneal opacity secondary

with HSV keratoconjunctivitis. five times daily are the various in neonatal or primary HSV
Trifluorothymidine 1% solution options. Neonates with HSV keratoconjunctivitis.
topically every 2 hours for 7 keratitis may also be treated with • Other bacterial conjunctivitis:
days and no longer than 21 days, topical cycloplegic agents for the Tetracycline 1% or erythromycin
adenine arabinoside 3% ointment relief of ciliary spasm. Topical 0.5% ointment every 4 hours for
or acyclovir 5% ointment given corticosteroids should be avoided 7 days is effective against Gram-

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Subspeciality-Cornea

positive cocci. MRSA neonatal Systemic complications of chlamydia review. Pediatric 1967;57:884-92.
conjunctivitis may be treated with conjunctivitis include pneumonitis 5. Wadhwani M, et al. Conjunctivitis in the
bacitracin 500 IU/g ointment, (10-20% cases), otitis, and pharyngeal
chloramphenicol 1% ointment or and rectal colonization, while that newborn—a comparative study. Indian J
vancomycin 5–31 mg/ml depending of gonococcal conjunctivitis include Pathol Microbiol. 2011;54(2):254–7.
upon bacterial sensitivity. arthritis, meningitis, anorectal 6. Meyer D. Ophthalmia neonatorum
Tobramycin 0.3% or ciprofloxacin infection, septicemia, and death. prophylaxis and the 21st century
0.3% ointment every 4 hours for antimicrobial resistance challenge.
7 days is effective against Gram- Prognosis is generally considered to be Middle East Afr J Ophthalmol.
negative bacilli. good in cases that are diagnosed early 2014;21(3):203-4.
• Fungal conjunctivitis: Natamycin and prompt medical therapy is initiated. 7. Gul SS, Jamal M, Khan N. Ophthalmia
5% drops hourly for 10–14 days, Most cases of infectious conjunctivitis neonatorum. J Coll Physicians Surg Pak.
or flucytosine 1% drops hourly for respond well to appropriate treatment; 2010 Sep;20(9):595-8.
10–14 days are recommended. however, morbidity and mortality 8. loto O, Gharaibeh A, Mezer E, Stankovic
increases due to systemic involvement B, Isenberg S, Wygnanski-Jaffe T.
Prophylaxis may require hospitalization and Ophthalmia neonatorum treatment
Ocular prophylaxis is largely aimed at intensive care. and prophylaxis: IPOSC global study.
preventing infected genital secretions Graefes Arch Clin Exp Ophthalmol.
of the mother from contaminating Key Points 2016 Mar;254(3):577-82.
the neonate’s eyes at birth. Antenatal • Development of ophthalmia 9. Mohile M, Deorari AK, Satpathy G,
screening in third trimester of Sharma A, Singh M. Microbiological
pregnancy to rule out herpetic, neonatorum can be prevented by study of neonatal conjunctivitis
chlamydial, or gonococcal infection is reducing the prevalence of sexually with special reference to Chlamydia
critical. Delivery by elective caesarian transmitted diseases and ensuring a trachomatis. Indian J Ophthalmol. 2002
section may be considered in cases of good antenatal and perinatal care. Dec;50(4):295-9.
active herpes lesions at delivery. 10. Palafox SKV, Jasper S, Tauber, Allyson
• Risk of complications can be D, Foster SC (2011) Ophthalmia
Pharmacological prophylaxis has minimized with prompt diagnosis Neonatorum. J Clinic Experiment
largely shifted from 2% silver nitrate and appropriate antibiotic therapy. Ophthalmol 2:119. doi:10.4172/2155-
drops to 2.5% povidone iodine, 9570.1000119.
1% tetracycline ointment, or 0.5% • Both the pediatrician and 11. David M, Rumelt S, Weintraub Z.
erythromycin ointment. Povidone ophthalmologist should be Efficacy comparison between povidone
iodine has been shown to be equal meticulously involved in the iodine 2.5% and tetracycline 1% in
efficacy as compared to the other agents, treatment. prevention of ophthalmia neonatorum.
with an added advantage of broad Ophthalmology. 2011 Jul;118(7):1454-8.
spectrum of action against all bacteria, References
fungi, chlamydia and viruses. 1. Lindquist Thomas D. Chapter 46 – Corresponding Author:

Ophthalmia Neonatorum. In: Cornea; Dr. Ritika Mukhija
Volume 1 - Fundamentals and Medical Dr. Rajendra Prasad Centre for Ophthalmic
Aspects of Cornea and External Disease. Sciences, All India Institute of Medical Sciences,
3rd ed. USA: Elsevier; 2011. p. 1222–34. New Delhi, India.

Complications and Prognosis 2. Ophthalmia neonatoum. BCSC
series: Pediatric Ophthalmology and
Ocular complications of neonatal Strabismus. American Academy of
conjunctivitis range from Ophthalmology; 2017.
thickened palpebral conjunctiva,
pseudomembrane formation,
3. Rao K, Ramji S, Thirupuram S, Prakash
K. Clinical and bacteriological study
peripheral pannus formation, of normal and inflamed neonatal
corneal edema and opacity to corneal
perforation and staphyloma formation. conjunctivae. Indian Pediatr
1992;29:161-5.
Untreated cases may even progress to
endophthalmitis and blindness. 4. Armstrong JH, Zacharias F, Rein HF.
Ophthalmia Neonatorum - A chart

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Subspeciality-Retina

Neurogenic and Vasculogenic
Components in Diabetic
Retinopathy

Richa Gupta MS, Sandeep Saxena MS, FRCSEd, FRCS, FRCOphth, FACS,FAMS. FAICO
Department of Ophthalmology, King George Medical University, Lucknow, India.

The 2015 International Federation changes in the retina - Neurogenic and activation of glial cells12.
Diabetes (IFD) reported that Diabetes Vasculogenic.
Mellitus (DM) affects 415 million Earlier studies have highlighted that
people worldwide1. Type-2 Diabetes Neurogenic serum homocysteine and Vitamin
Mellitus (T2DM) in particular has Newer evidence suggests an alternate D levels are associated with RNFL
already attained epidemic levels (80- pathway – the neurodegenerative thinning in DR13,14.
95% of the total diabetic population). damage, where the pathological
The risk of blindness is 2.4 times higher changes may begin in the neural layers Homocysteine is a by-product of
in an individual with diabetes. of the retina before any sign of vascular transmethylation reactions and is
Diabetic retinopathy (DR) is a retinal damage7-10. The neuronal degeneration detoxified by methionine synthetase,
microvasculopathy resulting from in DR is not localized but it is expected which depends on vitamin B12 and
prolonged hyperglycemia. The to affect the retina in global fashion folate as coenzymes for proper function.
prevalence of DR increases with the as per the metabolic nature of the Impaired activity of the enzyme
duration of diabetes and nearly all disease. The quality of vision begins to methylenetetrahydrofolate reductase
individuals with Type-1 and 60% of deteriorate much before the clinical raises the plasma levels of homocysteine
them with Type-2 DM develop some retinopathy becomes evident because result in apoptosis of retinal ganglion
retinopathy after 20 years2. Global the posterior pole has the most vital cell (RGC) by 3 pathways:
prevalence estimates indicate an overall structures related to visual function.
age-standardized prevalence of DR of yy Increase expression of pro-apoptotic
34.6%3. The prevalence rate of DR in The retinal nerve fibre layer (RNFL) protein Bax (Bcl-2-associated X
Indian Subcontinent is reported to be is composed of axons derived from protein)
from 12 to 37% in patients with Type-2 ganglion cells. Van Dijk et al. speculate
DM. an initial GCL loss in the pericentral yy Causes dysregulation of
Earlier, DR was considered solely a areas followed by RNFL thinning in the mitochondrial dynamics.
disease of retinal vasculature. Rodrigues peripheral macula11. RNFL thinning
et al.4 reported that neuroretinal changes is attributed to diabetes induced yy Homocysteine acts as an agonist
precede vascular signs in diabetes alterations in microcirculation viz. at the glutamate site of N-methyl
mellitus. They observed a significant leukostasis, vascular obliteration, and D-aspartate (NMDA) receptors,
thinning of the Ganglion cell layer (GCL) degenerative changes of the capillary causing the generation of free
and Retinal nerve fibre layer (RNFL) in basal membrane. Vasoconstriction, radicals thus induces apoptosis.
patients with diabetes mellitus with induced by diabetes, diminishes the
no DR. The hypothesis referring to blood supply from superficial capillaries Increased severity of retinopathy
the occurrence of neurodegeneration to the nerve fibre layer and optic nerve has been found to be associated with
before vascular damage has been head. Metabolic and oxidative stress of decreased average RNFL thickness that
confirmed by electrophysiological and diabetes leads to increased sensitivity can be attributed to increased levels of
psychophysical studies5,6. of the ganglion cell, which results in homocysteine.
Thus 2 pathways attributing to diabetic nerve cell loss (Figure 1). Chronic loss
of retinal neurons occurs due to the Vitamin D is a multifunctional
increased frequency of apoptosis and hormone. It has a suppressive role in
the pathogenesis of DR via its well-
recognized anti-angiogenic and anti-
inflammatory effects. It inhibits VEGF

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Subspeciality-Retina

Figure 1: Retinal Nerve Fibre Layer (RNFL) thickness analysis using optic disc cube of BRB17. This leads to an enhanced lipid
200 x 200 feature depicting on RNFL thickness deviation map a. left eye of patient with and protein exudation. Because these
non-proliferative diabetic retinopathy showing RNFL thinning, b. left eye of patient with exudates cannot penetrate the external
proliferative diabetic retinopathy showing thinning of RNFL. limiting membrane (ELM), they
accumulate anteriorly and lead to the
induced endothelial cell sprouting, pigment epithelial cells, pericytes, formation of an intraretinal edema due
elongation, and endothelial cell astrocytes, Muller cells, glial cells, to osmotic forces (as per Starling’s law).
proliferation. Enzymatic conversion and endothelial cells, functioning as Diffuse edema subsequently progresses
(hydroxylation) occurs in the liver signaling proteins, and involved in to the formation of intraretinal cystic
and kidney, causing activation of the angiogenesis15. The balance between spaces18.
vitamin D prohormone to the active VEGF and angiogenic inhibitors
form, calcitriol, which exerts its determines the proliferation of Resistive index of ophthalmic and
effect via nuclear receptors at several angiogenesis in diabetic retinopathy16. central retinal arteries
locations. Hypoxia, ischemia, accumulation
of oxygen free radicals, advanced Resistive index (RI) is a parameter
Vasculogenic glycation end products, and protein of vascular resistance, measured on
As described above, retinal kinase C have been implicated in the color Doppler. Blood supply to the
neurodegeneration causes early pathogenesis of diabetic macular edema retina is decreased due to biochemical
microvascular changes that include the (DME). These factors lead to increased and bio-molecular changes with
breakdown of the blood-retinal barrier, expression of VEGF-A. Elevated resultant retinal ischemia; this causes
vasoregression and impairment of levels of VEGF-A cause breakdown of increased blood flow in adjacent
neurovascular interaction. blood retinal barrier (BRB). Increased retinal capillaries, resulting in an
Vascular Endothelial Growth Factor vascular permeability is associated increase in vessel wall shear stress
(VEGF): VEGF is a part of a subfamily with concomitant decreased zonular which further causes increased vessel
of growth factors, secreted from retinal occludin-1, which is a main constituent diameter, leading to mechanical
injury to the vascular endothelium.
This circumferential stress results in
mechanical damage to the endothelium
and is directly proportional to the
perfusion pressure, vessel radius, and
inversely proportional to the thickness
of the vessel wall. Thus damage occurs
more on the vessel with larger diameter
resulting in further dilatation of vessels.

The tension resisting circumferential
stress in the vessel wall has an inverse
relationship with the radius of the
vessel, as a result, tension to counteract
circumferential stress is not attained
in a dilated vessel, and therefore there
is a tendency towards dilatation with
consequent hyperperfusion. As these
changes occur in retinal vasculature the
resistive index increases and also the
severity of the disease.

Inner 6 layers of the retina are supplied
by the Central retinal artery (CRA).
An increase in RI of CRA has been
observed19. Disorganization of retinal
inner layer (DRIL) involves four retinal
layers. An increase in RI of ophthalmic
artery impair the blood supply of retinal
pigmentary epithelium (RPE) resulting
in structural changes expressed as

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Subspeciality-Retina

Figure 2b: ETDRS grid macular thickness
map showing increased thickening in the
macular region.

Figure2a: SD-OCT in DME showing intraretinal cystic spaces in the inner nuclear layer. thickness is increased which on SD-
DRIL present with EZ disruption. OCT appears as an increased value
of CST and CAT further (Figure 2b)
topographical alterations in RPE on SD- corresponds with the anatomical causing deterioration of BCVA25. CST
OCT20. location of the ellipsoid fraction of is the preferred OCT measurement
the photoreceptors inner segment. for the central macula because of its
Spectral Domain OCT in DME The extent of the EZ disruption is higher reproducibility and correlation
Spectral-Domain Optical Coherence a predictor of visual outcome in with other measurements of the central
Tomography (SD-OCT) provides diabetic macular edema. macula.
high-resolution structural images
with precise retinal thickness yy DRIL - Failure to discriminate the An increase in CST and CAT is associated
measurements21. In a cross-sectional inner retinal layer boundaries; any of with increased odds of EZ disruption
image it shows Vitreomacular interface, the boundaries of ganglion cell layer- and these macular thickness parameters
DRIL, ELM and EZ (Ellipsoid Zone). inner plexiform (GCL-IPL) complex, serve as bioimaging biomarkers for
ETDRS grid highlights CST (Central and inner nuclear layer (INL) and EZ disruption in diabetic retinopathy.
Subfield Thickness) and CAT (Cube outer plexiform layer (OPL) (Figure Cystoid spaces extending from the
Average Thickness), 2a). DRIL was considered to be absent, INL to the OPL are accompanied by
if intraretinal cysts were observed in ELM disruption in DME, signifying
yy CST - Thickness of the central circle the outer nuclear layer, resulting in disturbance of the Muller cells. Muller
of diameter 1mm in the circular Early overall retinal thickening, but the cells lose their occludin content at
Treatment Diabetic Retinopathy inner retinal layers could still be the ELM level, which leads to cyst
Study (ETDRS) grid map. demarcated. DRIL in the 1-mm foveal formation. With increasing severity of
area has a detrimental effect on visual retinopathy, ELM disruption also leads
yy CAT - Overall average thickness for acuity (VA) and is predictive of VA in to increased grades of EZ disruption and
the internal limiting membrane- eyes with center-involved diabetic a decrease in BCVA.
retinal pigment epithelium tissue macular edema (DME). Early change
layer over the entire 6 x 6 mm square in DRIL prospectively recognizes Ellipsoid zone disruption was graded as;
scanned area. eyes with a high probability of Grade 0: Intact photoreceptor EZ; Grade
subsequent improvement or decline 1: focal disruption (subfoveal localized
yy ELM and EZ zone - The ELM separates in VA24. involvement) and Grade 2: Global
the layers of the rods and the cones disruption (generalized involvement
from the overlying outer nuclear Severity of retinopathy increases within the macular cube)24.
layer and is a linear confluence with the increment of serum VEGF
of junctional complexes between level. Significantly elevated levels of The presence of DRIL was observed
Muller cells and photoreceptors22,23. VEGF come into play even before the to be significantly associated with an
Ellipsoid zone (EZ) is the second evidence of DR. Raised level of VEGF increase in CST, CAT, and EZ disruption
hyper-reflective band, which further leads to DME, in which macular and a decrease in RNFL thickness. In

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Subspeciality-Retina

an earlier study, cases with DRIL have On follow up the severity of retinopathy Neuronal and glial cell abnormality as
been reported to be associated with can be detected by comparing current predictors of progression of diabetic
diminished retinal function compared retinal thickness to previously retinopathy. Curr Pharm Des 2007;
to those without DRIL. DRIL was graded documented baseline retinal thickness. 13:2699-712. [PMID: 17897014].
as Grade 0-DRIL absent; and Grade An increase in CST and CAT is
1-DRIL present. DRIL is considered imperative for an increase in VEGF. The 10. Mohr S, Xi X, Tang J, Kern TS. Caspase
to be absent if there is presence of advent of anti-VEGF pharmacotherapy activation in retinas of diabetic and
intraretinal cysts in the outer nuclear has increased the utilization of SD-OCT galactosemic mice and diabetic patients.
layer with overall retinal thickening in clinical practice for monitoring the Diabetes 2002; 51:1172-9. [PMID:
without disturbance in the integrity of treatment in DR. 11916941].
inner retinal layers. With increasing
severity of retinopathy, DRIL leads to References 11. van Dijk HW, Verbraak FD, Kok PH,
the destruction and stretching of its 1. Atlas D. International diabetes Garvin MK, Sonka M, Lee K, et al.
bipolar, amacrine, and horizontal cells, Decreased retinal ganglion cell layer
thus preventing the relay of information federation. IDF Diabetes Atlas, 7th thickness in patients with type 1
from photoreceptors to ganglion edn. Brussels, Belgium: International diabetes. Invest Ophthalmol Vis Sci.
cells resulting in RNFL thinning with Diabetes Federation. 2015. 2010;51:3660–5.
subsequent poor visual acuity26. 2. Fong DS, Aiello L, Gardner TW et al.
Retinopathy in diabetes. Diabetes 12. Takis A, Alonistiotis D, Ioannou
Conclusion care.2004;27 (suppl 1):s84-7 N, Kontou E, Mitsopoulou M,
The widespread availability of 3. Yau JW, Rogers SL, Kawasaki R, Papaconstantinou D. Follow-up of the
the patient-friendly imaging tool Lamoureux EL, Kowalski JW, Bek T, Chen retinal nerve fiber layer thickness of
complements the benefit of using SD- SJ, Dekker JM, Fletcher A, Grauslund J, diabetic patients type 2, as a predisposing
OCT based imaging biomarkers as Haffner S. Global prevalence and major factor for glaucoma compared to normal
reliable objective standard estimates risk factors of diabetic retinopathy. subjects. Clin Ophthalmol 2017;11:1135-
for early diagnosis and severity of the Diabetes care. 2012 Mar 1;35(3):556-64. 41
disease. 4. Rodrigues EB, Urias MG, Penha FM,
Badaró E, Novais E, Meirelles R, Farah ME. 13. Nadri G, Saxena S, Mahdi AA, Kaur A,
Cases with diabetes but no DR have been Diabetes induces changes in neuroretina Ahmad MK, Garg P, Meyer CH. Serum
demonstrated to be associated with a before retinal vessels: a spectral-domain vitamin D is a biomolecular biomarker
decrease in RNFL thickness, thereby optical coherence tomography study. Int for proliferative diabetic retinopathy.
signifying the neurodegeneration J Retina Vitreous. 2015;1:1. International journal of retina and
occurs prior to retinal vascular changes, 5. Nilsson M, von Wendt G, Brautaset R, vitreous. 2019 Dec 1;5(1):31.
therefore OCT-RNFL should be done for Wanger P, Martin L. Macular structure
early diagnosis of retinopathy. Not only and function and the development 14. Srivastav K, Saxena S, Mahdi AA, Shukla
increased severity of DR is associated of retinopathy in diabetes. Clin Exp RK, Meyer CH, Akduman L, Khanna VK.
with RNFL thinning but also with Optom. 2012;95:306–10. Increased serum level of homocysteine
increased serum homocysteine and low 6. Nilsson M, von Wendt G, Wanger P, correlates with retinal nerve fiber
vitamin D levels. Martin L. Early detection of macular layer thinning in diabetic retinopathy.
changes in patients with diabetes using Molecular vision. 2016;22:1352.
Resistivity index (RI) alteration of the Rarebit Fovea Test and optical coherence
ophthalmic artery and central retinal tomography. Br J Ophthalmol. 15. Gupta N, Mansoor S, Sharma A, Sapkal A,
artery was found to be prevalent among 2007;91:1596–8. Sheth J, Falatoonzadeh P, Kuppermann
patients with early changes in DR. 7. Lieth E, Barber AJ, Xu B, Dice C, Ratz MJ, BD, Kenney MC. Diabetic retinopathy
Tanase D, Strother JM. Glial reactivity and VEGF. The open ophthalmology
An increase in CST, CAT, EZ disruption, and impaired glutamate metabolism journal. 2013;7:4.
DRIL on SD-OCT was found to be in short-term experimental diabetic
associated with the increase in the retinopathy. Penn State Retina Research 16. Funatsu H, Yamashita H, Noma
severity of retinopathy and decrease in Group. Diabetes 1998; 47:815-20. [PMID: H, Shimizu E, Yamashita T, Hori
BCVA. SD-OCT is valuable in detecting 9588455]. S. Stimulation and inhibition of
subclinical retinal thickening in 8. Barber AJ, Lieth E, Khin SA, Antonetti angiogenesis in diabetic retinopathy.
advanced retinopathy without DME, DA, Buchanan AG, Gardner TW. Jpn J Ophthalmol 2001; 45:577-84.
which is recommended to be followed Neural apoptosis in the retina during [PMID: 11754898].
closely as they are at increased risk of experimental and human diabetes. Early
developing DME. onset and effect of insulin. J Clin Invest 17. Bhagat N, Grigorian RA, Tutela A,
1998; 102:783-91. [PMID: 9710447]. Zarbin MA. Diabetic macular edema:
9. Fletcher EL, Phipps JA, Ward MM, pathogenesis and treatment. Surv
Puthussery T, Wilkinson-Berka JL. Ophthalmol. 2009;54(1):1–32.

18. Zhang X, Zeng H, Bao S, Wang N,
Gillies MC. Diabetic macular edema:
new concepts in patho-physiology and
treatment. Cell Biosci. 2014;4:27

19. Khatri M, Saxena S, Kaur A, Bhasker SK,
Kumar M, Meyer CH. Resistive index
of ophthalmic artery correlates with

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retinal pigment epithelial alterations ultrahighresolution optical coherence journal of retina and vitreous. 2019 Dec
on spectral domain optical coherence tomography. Arch Ophthalmol 2003; 1;5(1):29.
tomography in diabetic retinopathy. 121:695-706. [PMID: 12742848]. 26. Sharma SR, Saxena S, Mishra N,
International journal of retina and Akduman L, Meyer CH. The association
vitreous. 2018 Dec;4(1):12. 23. Srinivasan VJ, Monson BK, Wojtkowski of grades of photoreceptor inner
M, Bilonick RA, Gorczynska I, Chen segment-ellipsoid band disruption with
20. Khatri M, Saxena S, Kumar M, Chabbra R, Duker JS, Schuman JS, Fujimotoet severity of retinopathy in type 2 diabetes
AK, Bhasker SK, Akduman EI, Pham H, JG. Characterization of outer retinal mellitus. J Case Rep Stud 2014;2:502.
Akduman L. Resistive index of central morphology with high-speed,
retinal artery is a bioimaging biomarker ultrahighresolution optical coherence Corresponding Author:
for severity of diabetic retinopathy. tomography. Invest Ophthalmol Vis Sci
International journal of retina and 2008; 49:1571-9. [PMID: 18385077]. Dr. Richa Gupta MS
vitreous. 2019 Dec 1;5(1):38. Department of Ophthalmology,
24. Sun JK, Lin MM, Lammer J, Prager S, King George Medical University,
21. Kiernan DF, Mieler WF, Hariprasad Sarangi R, Silva PS, et al. Disorganization Lucknow, India.
SM. Spectral-domain optical coherence of the retinal inner layers as a predictor
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22. Drexler W, Sattmann H, Hermann B, 25. Ahuja S, Saxena S, Akduman L, Meyer
Ko TH, Stur M, Unterhuber A, Scholda CH, Kruzliak P, Khanna VK. Serum
C, Findl O, Wirtitsch M, Fujimoto JG, vascular endothelial growth factor is
Fercher AF. Enhanced visualization a biomolecular biomarker of severity
of macular pathology with the use of of diabetic retinopathy. International

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Subspeciality-Oculoplasty

Siliconoma of Eyelid Following
Intravitreal Silicone Oil Insertion

Sapan Shah, Hetvee Gandhi, Aashka Shah, Bansari Patel
L.G. Hospital Ahmedabad, Gujarat, India

Abstract: Case report: Patient presented with complaint of right eye UL swelling forsince 1 month. Patient had was high
myopiac with history of trauma to right eye 6 months back which caused RD. RD repair with silicone oil implantation was
done, followed by SOR after 2 months. One1 month later phacotrab surgery was done. Patient investigated and operated for
mass removal with histopathology and it’s report was suggestive of silicone oil granuloma.
Conclusion: Silicone oil can migrate outside vitreous cavity to reach extra ocular tissues.
Keywords: Upper lid, retinal detachment, silicone oil removal.

Silicone oil has been widely used Figure 1: Image of patient showing swelling and ptosis in the right eye upper lid.
for decades in complex vitreoretinal
surgeries. Silicone oil was first injected Figure 2: CT scan plate showing well circumscribed, non enhancing, hyperdense area in
into the vitreous cavity of rabbit eyes upper lid.
in 1958, and then utilized for the
treatment of retinal detachment in 1962 tear and retinal detachment in his right glaucoma surgery after 1 month as the
by Cibis et al.1 Several complications eye 6 months back due to trauma. He patient had high intraocular pressure
of intravitreal silicone oil insertion underwent right eye retinal detachment and cataractous changes which may be
have been reported: including cataract repair with silicone oil implantation as attributed to silicone oil implantation
formation, rubeosis iridis, optic tamponade. After 2 months of surgery which was done along with vitrectomy.
neuropathy, glaucoma, chronic uveitis, silicone oil removal was done. Followed On examination his best corrected
migration into the lateral ventricles by this the patient was operated for visual acuity in right eye was 6/36
of the brain, posterior ciliary artery cataract extraction along with anti-
occlusion, epiretinal membranes,
subconjunctival, and orbital foreign
body granuloma2-5. However, to our
knowledge, there are only 7 cases
reported by The British Journal with
intraocular silicone oil migration
into upper eyelid causing ptosis as a
postoperative complication6-7. Herein,
we report a case which presented to our
hospital with such rare complication.

Case Report
A 33 year male shopkeeper by profession
presented with non painful swelling
gradually increasing in size over right
upper eyelid leading to ptosis (Figure
1) since 1 month. On detailed history
taking it was found that the patient was
high myopic and had a large horse shoe

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Subspeciality-Oculoplasty

and left eye 6/9 with facial symmetry Figure 3: Intraoperative picture showing jelly like structure identified on separating the
and no abnormal head posture. He orbicularis muscle.
had a swelling on right upper lid
temporal region which was firm, well
defined, non tender and movable
which caused mechanical ptosis. Our
provisional diagnosis was a lacrimal
gland lymphoma as there was mild
conjunctival chemosis with salmon
patch appearance. CT scan was done
which demonstrated a circumscribed
non-enhancing hyperdense area in
right upper eye lid supporting our
provisional diagnosis (Figure 2), but
blood counts and peripheral smear
examination were normal. After taking
an informed consent an excisional mass
biopsy was planned. Right eye upper lid
was marked for about 25mm * 5mm at
lid crease. Incision made on lid crease,
orbicularis separated and large jelly like
structure identified (Figure 3). Mass
was removed in toto which was 20mm
* 5mm in size (Figure 4) and sent for
histopathological examination. Wound
closure was done with vicryl 6-0 and
pad and patch done. Post operative
day 1 patient had no complaints, had a
healthy wound with no wound gaping,
bleeding or discharge and patient
was discharged with topical and oral
antibiotics and serratiopeptidase for
one week.

Histopathological examination was
suggestive of fibrous tissue with focal
giant cell reaction to clear cell vacuoles,
suggestive of a foreign body granuloma
possibility of silicone oil granuloma.

On 3rd week follow up examination
there was no residual swelling or ptosis,
both eyelid height and contour were
satisfactory, and the patient was satisfied
with the cosmetic improvement .

Discussion Figure 4: 20 mm *5 mm granuloma removed in toto.
The uUse of silicone oil is an established
method of applying tamponade in to prevent its anterior and posterior is rare complication of intravitreal
treating vitreoretinal diseases such segment complications such as cataract, silicone oil insertion. Very few cases
as retinal detachments, proliferative glaucoma, corneal decompensation, of silicone oil migration into the
diabetic retinopathy associated with optic neuropathy, retinal toxicity, or subconjunctival space, eyelid, optic
tractional retinal detachments.8 extra ocular migration. The migration nerve and brain have been reported9-
Intravitreal silicone oil is intended to be of silicone oil in extraocular tissues 10. There have been 3 cases of silicone
removed after several weeks to months

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Subspeciality-Oculoplasty

oil intrusion in the upper eyelid 1, ocular surgery should be evaluated as caused by silicone oil. Am J
8, and 19 years after vitreoretinal such swellings may be due to chronic Ophthalmol2005;140:934-936.
surgeries, and Nazemi et al.7 reported inflammatory reaction causing a 8. G. Morphis, C. Irigoyen, A. Eleuteri, T
1 case of subconjunctival silicone oil foreign body granuloma which should Stappler, I. pearce, and H. Heimann,
granuloma where probably the silicon be an important differential diagnosis. “Retrospective review of 50 eyes with
oil might have migrated through the long term silicone oil tamponade
Ahmed glaucoma valve. Srinivasan References for more than 12 months, “Graefe’s
et al. described 2 cases of episcleral Archive for clinical and Experimental
granulomas adjacent to vitrectomy 1. CibisP, Becker B, Okun E, Canaan S, Ophthalmology. Vol. 250, pp. 645-652,
entry sites suggesting possibility of The use of liquid silicone in retinal 2012.
extraocular migration through tracts detachment surgery. Arch ophthalmol. 9. P.P.Nazemi,L.P.Chong,R.Varma,andM.
formed by vitrectomy ports. These 1962;68:590-9. A. Burnstine, “ Migration of intraocular
studies have shown extraocular silicone silicone oil into the subconjunctival
oil migration as a delayed complication 2. Shin H, Lemke BN, Stevens TS , Lim MJ, space and orbit through an Ahmed
ranging from 1 to 19 years and the posterior ciliary – artery occlusion after glaucoma valve.” The American Journal
possible path of migration of silicone subcutaneous silicone-oil injection. Ann of Ophthalmology. Vol. 132, no. 6, pp.
oil has been suggested as sclerotomy Ophthalmol. 1988;20:342-4. 929-931, 2001.
sites created for vitrectomy or through 10. J. Biswas, P. S. Bhende, L. Gopal, S, Parikh,
the transscleral implant. 3. FedermNjl, Schubert HD. Complications and S. S. Badrinath, “subconjunctival
associated with the use of silicone oil in cyst following silicone oil injection: a
Our case demonstrates a silicone oil 150 eyes after retina-vitreous surgery. clinic pathological study of five cases”,
granuloma in right eye upper lid which Ophthalmology. 1988;95:870-6. Indian journal of ophthalmology, vol.
developed rapidly within 6 months of 47, n o 3, pp 177-180, 1999.
silicone oil implantation after retinal 4. Srinivasan S Singh AK, Desai SP,
detachament repair even though the Talbot JF , Parsons MA . Foreign body Corresponding Author:
patient had underwent silicone oil episceral granuloma complicating
removal 2 months post insertion. intravitreal silicone oil tamponade. Dr. Hetvee Gandhi
There might have been silicon oil A clinicopathological study. L.G. Hospital Ahmedabad,
particle migration into subconjunctival Ophthalmology 2003;110:1837-40. Gujarat, India
space through scleral suture sites post
vitrectomy or of the phacotrab surgery 5. Lee JH, Kim YD, Woo KI, Kong M.
which through lymphatics post phaco- Subconjuctival and orbital silicone oil
trab or through an artificial tract due to granuloma (Siliconoma) complicating
peribulbar injections might have found intravitreal silicone oil tamponade. Case
its way into the upper eyelid. Hence Rep Ophthalmol Med. 2014 : 1-4
while dealing with cases of mechanical
ptosis, detailed history of trauma and 6. QuintynJC,GenevoisO,RantyML,Retout
A; Silicone oil migration in the eyelid
after vitrectomy for retinal detachment.
Am J Ophthalmol2003;136:540-542.

7. Donker DLT, Paridaens D, Mooy CM,

vanden Bosch WA: Blephroptosis
and uppereyelid swelling due to
lipogranulomatous inflammation

42 DOS Times - Volume 25, Number 5, March-April 2020 www.dosonline.org/dos-times

Subspeciality-Comprehensive Ophthalmology

An Overview of Artificial
Intelligence in Ophthalmology

Ekta Singla, Parul Ichhpujani , Suresh Kumar
Department of Ophthalmology, Government Medical College and Hospital, Chandigarh, India

With the advancement in technology, labeled clinical features. macular degeneration (ARMD), etc., AI
human race has advanced as well based DL can be used for narrowing the
leading to an increase in the life DL, also referred to as the “unsupervised gap between health care system and
expectancy. This multiplying aging learning” is the new AI technique the clinical demand. For the real-world
population have added to the load of all which bypasses the need for labeling by implementation two models have
physicians including ophthalmologists the health care provider. DL works on been suggested: “the fully-automated”
across the world to provide adequate the principle of deep neural networks and the “semi-automated”. The fully
health services at the population level. modeled after human brain which automated model would itself triage
Limited availability of infrastructure are used to recognize a pattern. DL the patient whether they need to
(eye clinics and hospitals) and eye “self-learns” the pointing features to see an ophthalmologist or continue
care providers (Ophthalmologists and classify a disease or its severity by using community-based monitoring without
optometrists) results in long waiting the entire images with their clinical any human involvement. On the other
time to see an ophthalmologists. diagnosis. There are mainly two types hand,the semi-automated model would
This results in irreversible visual of DL programs: convolutional neural require the help of a human assessor to
loss especially in resource deprived, network (CNN) and massive-training augment DL to triage the patients4.
developing nations. The need of the artificial neural network (MTANN).
hour is to look for solutions to increase CNN and MTANN, just like human This semi-automated model of DL has
the accessibility and availability of eye brain, consist of multiple interconnected successfully been used by Xie et al5 in
care services. Artificial Intelligence (AI) layer of neurons designed to simulate Singapore for screening DR whereby
offers a plausible solution. “thinking”. An input is fed into first the AI triaged the patients using colored
layer whose output serves as an input fundus photographs and those flagged
What is Artifical Intelligence? for the next layer. The analysis from as abnormal were then graded by expert
The phrase “Artificial intelligence” each layer is transmitted to the network ophthalmologists.
was first coined by John McCarthy in until final outcome is produced. For
19551. The simplified meaning of AI is an image-based diagnosis, a CNN Applications of AI in
to accomplish tasks using advanced algorithm teaches itself by analyzing Ophthalmology
computers with minimal human pixel or voxel intensities in a labeled Advanced ophthalmology practice
involvement. Its aims to simulate the training set of expert-graded images involves use of multimodal imaging
human behavior. and then provides a diagnostic output devices and hence is the perfect platform
at the top layer. This process is repeated to implement AI for improving the
AI is a broad term encompassing several times for every image. Once the patient care. This is reflected by the
multiple components of which machine algorithm optimizes itself, it can work fact that in 2018, FDA approved the first
learning (ML) and deep learning (DL) on unknown images. However, the ophthalmic AI machine, IDx-DR, for the
are the two major components. The use convolutional operations are carried on screening of DR (Figure 1)6.
of AI in ophthalmology began with the within the network in CNN, whereas in
traditional ML technique also referred MTANN they are outside the network3. AI mainly works by utilizing colored
to as the “supervised learning,” as fundus photographs (CFP) and optical
described by Ruamviboonsuk et al.2 In How Can AI Be Implemented for coherence tomography (OCT) images in
ML technique, the health care provider Ophthalmology Diagnosis and ophthalmology. DL have been applied
labels the individual clinical features Screening? to major ophthalmic diseases such as
and severity in the images to help AI DR, ARMD, glaucoma and ROP. Role of
develop an algorithm which can be With increasing burden of the common AI for various ophthalmic disorders is
used to classify images based on those ophthalmological diseases such as being addressed underneath:
diabetic retinopathy (DR), age related

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Subspeciality-Comprehensive Ophthalmology

health care professionals including
ophthalmologists, optometrists,
general physicians using direct as well
as indirect ophthalmoscopy, slit lamp
examination, fundus cameras and OCT.
AI has revolutionized the technique of
DR thus aiding in increased accessibility
and availability of care for the patients.

Table 1 shows the specificity and
sensitivity of various DL algorithms
used worldwide for diagnosing
referable DR (> moderate NPDR or
worse including diabetic macular
edema) based on fundus photographs.

b) AI In ARMD
By the year 2040, the world is expected
to have 288 million patients of ARMD
of which 100% may have intermediate
ARMD or worse14. Hence these patients
need to be screened timely for adequate
referral to tertiary care centres. Various
DL algorithms based on fovea centered
images are being used to screen
ARMD with acceptable sensitivity and
specificity (Table 2).

Figure 1: IDxDR Machine. c) AI In Glaucoma
Glaucoma is expected to affect 112
Table 1: Specificity and sensitivity of various DL algorithms for Diabetic million people globally by the year
Retinopathy 202017. Timely diagnosis, monitoring
structural as well as functional
DL System Authored By Senstivity (%) Specificity (%) progression and titration of the
treatment at various time points
Abràmoff et al8 (2016) 96.80 87 can help prevent permanent visual
disability.
Gulshan et al9 (2016) 87 98.5
Using DL algorithm, optic nerve head
Gargeya and Leng10 (2017) 96.3 92.1 cupping has been estimated by Li et al18
and Ting et al 11 with sensitivity and
Ting et al11 (2017) 100 81.3 specificity ranging from 92-96%. ML
based algorithms have been applied
Abràmoff et al6 2018(IDx-DR) 87.2 90.7 successfully to predict structural and
functional damage in glaucoma19.
Natarajan et al12 (2019) 100 84 Yousefi et al have developed a ML
based algorithm which predicts visual
Varadarajan13 (2020) 85 80 field progression earlier than the
conventional strategies.
Table 2: Specificity and sensitivity of various DL algorithms for ARMD
Intraocular pressure (IOP) lowering
DL System Authored By Senstivity (%) Specificity (%) is considered to the only effective
treatment in slowing down the
Ting et al11 (2017) 93.20 88.70 disease progression20. Kazieman et al
have developed an algorithm based
Burlina et al15 (2017) 90.3 89.2

Grassmen et al16 (2018) 84.20 94.30

a) AI In DR DR.7 Screening for DR with timely
By the year 2040, nearly 600 million referral and management is the key
people will have diabetes mellitus to prevent blindness. DR screening
with about one-third of them having across the world is done by many

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Subspeciality-Comprehensive Ophthalmology

on tonometry and visual field data
to predict the rate of progression of
glaucoma at different IOP values21.

d) AI In Retinopathy of Figure 2: Black Box. these formulas have shown promising
Prematurity (ROP) results32.
ROP is the leading cause of childhood using slit lampbased photographs.
blindness in the world. Early screening First step involves recognition of f) Miscellaneous
can help prevent blindness from mydriatic versus non-mydriatric and Other major areas where applicability
the disease22. The main barriers in optical section versus diffuse slit lamp of AI is being researched includes
screening is its subjective nature and based photographs. The second step amblyopia, retinal vascular occlusions,
secondly the limited availability of ROP comprises categorizing as normal (no retinal detachment and corneal ectasias
trained professionals. DL together with cataract), cataractous or postoperative such as keratoconus.
tele-ophthalmology can offer novel IOL. And finally, if cataract is detected,
solutions. Brown et al23 developed an the type and severity of cataract using Challenges with AI
automated DL system to diagnose PLUS LOCS II is done.28 Accordingly, the Despite the high level of accuracy
disease of ROP with promising results. patient is referred to the tertiary eye care of AI based algorithms, there are
Similarly, the iROP DL algorithm centre. The sensitivity and specificity certain challenges which needs to be
reported a sensitivity and specificity of this algorithm for cataract detection addressed. Foremost the data used
of 100% and 94%, respectively, in has been reported to be 92% and 83%, is not from a heterogeneous group
predicting pre-plus or worse forms of respectively27. of population. Applying the same
ROP24. It is expected that this system set of images to the population can
could also develop a severity scoring Li et al29 developed a DL based result in erroneous results. Hence,
system to monitor the progression, algorithm for diagnosing the cataract diversifying the data set in terms of
regression and treatment protocols. using colored fundus photographs. The ethnicities may help in resolving the
visibility of fundus images was used to issue. Secondly, disorders like ROP and
e) AI In Cataract grade cataract into four categories (non Glaucoma have large inter-observer
AI in the field of cataract has been cataract, mild, moderate and severe variations. Too little data is available
relatively much less explored compared cataract). The system achieved an AUC for certain common diseases(cataract)
to other counterparts. Till date cataract (area under curve) of 97.2% for cataract and certain uncommon diseases (ocular
is diagnosed by the ophthalmologists detection, and 87.7% for severity tumors). The AI tool learns from what
using slit lamp and graded according grading. is presented to it. Hence if the dataset
to classifications such as the Lens is small or not representative of real
opacity classification system (LOCS Likewise, for IOL power calculation time population it is likely to produce
III)25. Firstly, this process requires AI based formula “The Ladas Super” inaccurate results.
clinical expertise and secondly, it is an Formula was derived by extracting
subjective assessment. features from respective “ideal The complex CNN which makes AI a
portions” of existing formulas (namely, powerful tool fails to explain how the
Similarly, intraocular lens (IOL) Hoffer Q, Holladay-1, Holladay-1 system reaches the conclusions it does-
power calculation for cataract surgery with Koch adjustment, Haigis, and something referred to as “black box”
is mainly based on axial length and SRK/T formulas) and plotted into a phenomenon. Black-box is basically an
keratometry catering to the eyes with 3-D surface30. Apart from optimizing opaque object which converts input
normal values, without considering formula selection process, AI has also into output without being aware of
the abnormal profiles (post-LASIK, been used to develop algorithms for IOL the underlying processing mechanism
keratoconus, etc.). To overcome these power calculation. One such method (Figure 2). Researches are discovering
short comings, AI algorithms using is the Hill-Radial Basis Function (RBF) how to peer into this black box. To
both ML and DL have been developed26. method which has been obtained on untangle the mystery, researchers have
algorithm based on measurements used the black masks to shield parts of
Cataract grading using AI algorithms obtained from the Haag-Streit
takes into consideration either slit lamp- LENSTAR optical biometer31. Similarly
based photographs or colored fundus another formula is Kane formula. Both
photographs. Wu et al27 in a large-scale
study in China have recently developed
a 3-step sequential algorithm based on
DL for diagnosis and referral of cataract

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Subspeciality-Comprehensive Ophthalmology

retinal images from the AI algorithm Pac J Ophthalmol (Phila) 2020; 9:78–84. learning. accepted for publication in
to discover how such masking affected Nature Communications. Nat Commun
the system’s working. This may also 3. Kappor R, Walters SP, Al-Aswad 2020; 11:130.
help them in looking for areas in AI LA, The Current State of Artificial
accounting for the process of decision Intelligence in Ophthalmology, Survey 14. Wong WL, Su X, Li X, et al. Global
making33. of Ophthalmology.2018;64(2): 233-40. prevalence of age-related macular
There is a fear that AI might de-skill degeneration and disease burden
the physicians in decision making 4. Gunasekeran, Dinesh Visva et al projection for 2020 and 2040: a
and forming opinions in the future. AI Artificial Intelligence in Ophthalmology systematic review and metanalysis.
doesn’t consider the psychological and in 2020: A Technology on the Cusp for Lancet Glob Health 2014;2:e106–16.
social aspects of human nature which Translation and Implementation, Asia-
a skilled physician would normally Pacific Journal of Ophthalmology. 2020; 15. Burlina PM, Joshi N, Pekala M, et al.
account for. Moreover, most currently 9 (2):61-66. Automated grading of age-related
used AI machines are capable of macular degeneration from color
monitoring only a single disease at a 5. Xie Y, Nguyen Q, Bellemo V, et al. Cost- fundus images using deep convolutional
time. Switching between different AI’s effectiveness analysis of an artificial neural networks. JAMA Ophthalmol
for different diseases is not feasible for intelligence-assisted deep learning 2017;135:1170–6.
the physicians specially at community system implemented in the national tele-
level where resources are already scarce. medicine diabetic retinopathy screening 16. Grassmann F, Mengelkamp J, Brandl
Lastly, the lack of infrastructure in Singapore. Invest Ophthalmol Vis Sci C, et al. A deep learning algorithm for
for implementing the AI system is 2019; 60:5471. prediction of age-related eye disease
major concerning issue especially in study severity scale for age-related
developing countries where internet 6. Abramoff MD, Lavin PT, Birch M, et macular degeneration from color
supply is limited. al. Pivotal trial of an autonomous AI- fundus photography. Ophthalmology
based diagnostic system for detection 2018;125:1410–20.
Conclusion of diabetic retinopathy in primary care
Despite all these challenges, AI has offices. NPJ Digit Med 2018.139 17. Tham YC, Li X, Wong TY, et al. Global
shown very promising results in prevalence of glaucoma and projections
expanding the ophthalmic health care 7. Ting DSW, Pasquale LR, Peng L, et al. Br J of glaucoma burden through 2040: a
facilities. It can potentially reduce the Ophthalmol 2019;103:167–175 systematic review and meta-analysis.
barriers to access the ophthalmic health Ophthalmology 2014;121:2081–90.
care systems and hence can prevent 8. Abràmoff MD, Lou Y, Erginay A, et
avoidable blindness. Future research al. Improved automated detection of 18. Li Z, He Y, Keel S, et al. Efficacy of a
on the black box nature of AI, its diabetic retinopathy on a publicly deep learning system for detecting
transparency, liability, issues related to available dataset through integration of glaucomatous optic neuropathy
cyber security, clinical deployment and deep learning.Invest Ophthalmol Vis Sci based on color fundus photographs.
the cost effectiveness may help in better 2016;57:5200–6. Ophthalmology 2018;125:1199–206.
understanding and implementation. AI
is on the brink of bringing paradigm 9. Gulshan V, Peng L, Coram M, et al. 19. Christopher M, Belghith A, Weinreb
shift in the ongoing clinical practice Development and validation of a deep RN, et al. Retinal nerve fiber layer
and services in the upcoming future. learning algorithm for detection of features identified by unsupervised
Last but not the least, remember that AI diabetic retinopathy in retinal fundus machine learning on optical coherence
does not intend on replacing the human photographs. JAMA 2016;316:2402–10. tomography scans predict glaucoma
race. progression. Invest Ophthalmol Vis Sci
10. Gargeya R, Leng T. Automated 2018;59:2748–56.
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1. McCarthy J, Minsky ML, Rochester N, using deep learning. Ophthalmology 20. Yousefi S, Kiwaki T, Zheng Y, et al.
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Summer Research Project on Artificial 11. Ting DSW, Cheung CY, Lim G, et al. learning. Am J Ophthalmol 2018;193:71–
Intelligence, August 31, 1955. For: AI Development and validation of a deep 9.
Magazine2006;2712–14 learning system for diabetic retinopathy
2. Ruamviboonsuk P, Cheung C.Y, and related eye diseases using retinal 21. Lichter PR, Musch DC, Gillespie BW,
Zhang X, et al. Artificial intelligence in images from multiethnic populations et al. Interim clinical outcomes in
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diabetic macular edema grades from Automated diagnosis of plus disease in
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retinopathy of prematurity using deep Br J Ophthalmol 2019; 103:1553–1560. Kane formula with existing formulas for
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Basics

Ocular Changes During Pregnancy

1Dr. Anwara Mammel MS, 1Dr. Amrit Mandal MS, 1Dr. Shreya Gujral MBBS,
2Dr. Harman Preet Kaur MBBS, 1Dr. Manav Deep Singh MS
1. Atal Bihari Vajpayee Institute of Medical Sciences and Dr. R.M.L. Hospital, New Delhi, India.
2. Palika Maternity Hospital, Lodhi Colony, New Delhi, India.

Abstract: Pregnancy causes significant changes in all systems of the body. The ocular effects of pregnancy may be physiological
or pathological or may be modifications of pre-existing conditions. The physiological changes include increased pigmentation
around eyes, changes in the refractive status, decrease in corneal sensation, dry eye and transient loss of accommodation. Pre-
existing diseases like Grave’s disease, Optic neuritis should be monitored due to their remission or relapse during pregnancy.
There may be worsening of diabetic retinopathy, development of pituitary adenoma and increased chances of venous
sinus thrombosis during pregnancy. Pregnancy related diseases like pre-eclampsia and eclampsia can lead to hypertensive
retinopathy, exudative retinal detachment and cortical blindness. Use of ophthalmic drugs can affect fetal health. Knowledge of
physiological changes and diagnosing the eye diseases that may develop during pregnancy and thereby treating and preventing
these diseases are important for the safety of both mother and the child.

Pregnancy affects all organ systems Unilateral ptosis has been reported refractive surgery during pregnancy is,
including the eye and visual system. during pregnancy and following thus, contraindicated.
A wide variety of physiological and normal delivery believed to be resulting Lens
pathological changes may occur in the from hormonal and fluid effects on the Studies have reported transient loss of
eye during pregnancy. levator aponeurosis1,2. accommodation both during pregnancy
Tear film and lactation. Increase in lens curvature
The ocular effects of pregnancy can Pregnancy can affect tear film may cause a myopic shift.
be divided into the following five physiology and result in dry eye Intraocular pressure (IOP)
categories: syndrome. This is caused by increased Pregnancy is associated with a
immune reaction in the lacrimal duct relative decrease in IOP in healthy
yy Physiological ocular changes that cells and direct destruction of acinar women, ocular hypertensive as well
develop during pregnancy cells by prolactin, transforming growth as glaucomatous subjects. As the
factor beta-1 and epidermal growth pregnancy advances, IOP declines
yy The effects of pregnancy on pre- factor. with statistically significant decrease
existing eye disorders Cornea from first to third trimester. Various
Corneal sensitivity tends to decrease mechanisms put forward to explain
yy Disorders of the eye associated with specially during the latter part of this IOP drop include hormone induced
pregnancy related diseases pregnancy and it usually returns to blockade of ocular hypertensive effect of
normal by eight weeks postpartum. endogenous corticosteroids, decreased
yy Neuro-ophthalmological changes in Corneal oedema occurs that leads episcleral venous pressure resulting
pregnancy to an increase in corneal thickness. from decreased systemic vascular
Studies have also reported an increase resistance, lower scleral rigidity during
yy Disorders related to labor and in corneal curvature during pregnancy gestation1-3. Mild metabolic acidosis
delivery that resolved completely following during gestation results in decreased
delivery or breast feeding. Increase in production of aqueous which in turn
Physiological Changes During corneal thickness due to edema can also contributes to decrease in IOP4,5,6.
Pregnancy decrease the refractive index of the A study evaluating the effect of
Eyelids cornea, causing a hyperopic shift. A

Reversible pigmentation around
the eyes known as melasma, the
most common ocular physiological
change. It is thought to be attributed
to hormonal changes and increased
melanin synthesis during pregnancy.

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Basics

progesterone and beta human develop. Indications for surgery during third trimester is associated with the
chorionic gonadotropin (HCG) on pregnancy include tractional retinal lowest activity of the disease which
aqueous dynamics during pregnancy detachment, non-resolving vitreous might help by tapering the systemic
has concluded that the progesterone hemorrhage and neovascular glaucoma. immunosuppressive medications.
level, but not the beta HCG level, was Glaucoma
correlated with IOP, aqueous flare and In general, pre-existing glaucoma Grave’s disease
corneal thickness7. It also stated that improves during pregnancy due to
aqueous flow remains constant during a fall in IOP as mentioned earlier. If It is the most common cause of
and after pregnancy, but IOP decreases possible, anti-glaucoma medications hyperthyroidism during pregnancy.
due to an increase in outflow facility. may be withheld in pregnant patients. It tends to remit late in pregnancy and
However, in some females it is difficult relapse postpartum. Thyroid inhibitors
Visual fields to regulate IOP in spite of maximal like propylthiouracil, methimazole
medical therapy. Extensive counselling and carbimazole all cross placenta and
The classical field change is a bitemporal along with the involvement of are excreted in breast milk, but the
hemianopia. However, visual field obstetrician and anaesthetist is desired drug of choice in pregnant women is
changes varying from slight temporal in the decision making process for best propylthiouracil10.
or concentric contraction to complete outcomes. Patient should be clearly
homonymous hemianopia have been informed about the benefits, risks and Disorders of the Eye Associated
reported. The asymptomatic visual field potential adverse effects of the therapy with Pregnancy Related Diseases
changes were shown to be completely along with alternative strategies. Pre-eclampsia and eclampsia
reversible postpartum. Central serous chorioretinopathy
High level of cortisol during pregnancy Pre-eclampsia usually occurs after fifth
Immunity is thought to be responsible for month of pregnancy but may present
the increased risk of CSCR, mostly anytime between 3rd and 9th month.
Pregnancy, being an immun- observed in the third trimester8. Ocular Eclampsia occurs in upto 2% of women
ocompromised state, is linked with manifestations include blurred vision, with pre-eclampsia. It is an obstetrical
lower flare up rates of non-infectious visual loss or scotoma in the central emergency and prompt delivery of fetus
uveitis compared to non-pregnant state. visual field. Most patients recover and placenta is the only cure. Retinal
spontaneously within three months changes are likely to occur when systolic
The Effects of Pregnancy in Pre after delivery. and diastolic blood pressures are above
Existing Eye Disorders Ocular toxoplasmosis 150 and 100 respectively. The three
Diabetic Retinopathy Toxoplasmic retinochoroidis is the most common visual complications are
most common cause of posterior uveitis hypertensive retinopathy, exudative
There is an increased risk of development in immunocompetent patients. Primary retinal detachment and cortical
and progression of diabetic retinopathy infection during pregnancy may result blindness11.
during pregnancy. Various factors in congenital infection. Latent infection
influencing progression include may reactivate during pregnancy in Hypertensive retinopathy is the
the pregnant state itself, duration mother. most common manifestation of pre-
of diabetes, degree of retinopathy Uveal tumors eclampsia and eclampsia occurring
at time of conception, metabolic Choroidal hemangiomas have been in upto 60% of patients. The degree of
control of diabetes and the presence reported to undergo rapid growth retinopathy correlates with severity of
of co-existing hypertension and during pregnancy but some can regress eclampsia12.
hypercholesterolemia. An important postpartum9.
risk factor for the progression of the Uveitis Exudative retinal detachment is thought
diabetic retinopathy during pregnancy Improvement of some autoimmune to be caused by the choroidal ischaemia,
is the degree of retinopathy prior to diseases such as non-infectious uveitis, it occurs in 1% of preeclamptic patients
conception. Strict glycaemic control especially from the second trimester and upto 10% of eclamptic patients.
should be attained before conception.2 onwards has been observed. The The prognosis is good with resolving of
Incidence of severe congenital visual symptoms and retinal pigment
malformation and fetal death is epithelial (RPE) changes within weeks
higher in patients with proliferative of delivery13,14.
changes. If progression of the eye
disease is noted during pregnancy, Cortical blindness can present both
prompt laser photocoagulation is ante and postpartum occurring in
indicated in eyes with severe non- upto 15% of both pre-eclamptic and
proliferative changes and should not eclamptic patients. The symptoms
be delayed till proliferative changes include headache, seizures and loss of

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Basics

consciousness. Findings in MRI include demonstrates accelerated growth that stress on mother resulting in many
hyperintense signals on T2 weighted may cause acute visual symptoms20,21. reversible and potentially irreversible
images and hypointense signals on T1 In the event of severe visual loss in a pathological changes. The knowledge
weighted images in the occipital cortex. pregnancy close to term, immediate and early recognition of these can
These findings are consistent with the delivery of the fetus followed by the significantly reduce maternal as well as
transient ischaemic events as a result of surgical resection of the tumor should neonatal morbidity.
cerebral edema11,15,16,17. be considered. Symptomatic patients
presenting early in pregnancy medical References
HELLP Syndrome occurs in 10% of therapy with steroids and hyperosmotic 1. Yeneral NM, Kucumen RB. Pregnancy
women with severe pre-eclampsia. agents help to reduce the cerebral
Ocular findings include bilateral edema. and the eye. Turk J Ophthalmol 2015;
serous detachment with yellow/ white 45(5):213-19.
subretinal opacities and vitreous Benign intracranial hypertension
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with field defects being the most in pregnancy, what to expect? An in-
Disseminated intravascular coagulation common visual disturbance. It does depth review. Oman J Ophthalmol 2013;
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hypercoagulable state and can affect pregnancy.
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Neuro-Ophthalmic Changes in sclerosis must be considered as an Surv Ophthalmol 1988; 32:219-38.
Pregnancy etiology for acute puerperal lactation
Pituitary tumor associated blindness when there is no 5. Horven I, Gjonnaess H. Corneal
clear anatomic or infectious cause. indentation pulse and intraocular
The pituitary gland demonstrates pressure in pregnancy. Arch Ophthalmol
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The weight increases by 30% and Delivery
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in the form of pituitary adenoma.19 Pituitary apoplexy occurs as a result medications in pregnancy. Rev
Headache is the first presenting of ischemic pituitary necrosis due Ophthalmol 2000; 2000:91-99.
symptom followed by visual field to severe postpartum hemorrhage.
disturbances, bitemporal hemianopia Enlargement of pituitary gland, small 7. Ziai N, Ory SJ, Khan AR, Brubaker RF.
being the most common. Harboring an sella size, disseminated intravascular Beta-human chorionic gonadotropin,
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Summary
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physiological state with extensive in pregnant women and their offspring.
Meningiomas occur more often Endocr Pract 1996; 2(1):53-61.
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12. Tadin I, Bojic L, Mimca M, Karelovic
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13. Sheth B, Mieler W (). Ocular
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